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Biomedical subjects

M Fiedler

Publications and source records attributed to M Fiedler.

32 records · Page 2Linked to original sources
PubMed2000

Human papillomavirus type 16 E7 oncoprotein binds and inactivates growth-inhibitory insulin-like growth factor binding protein 3.

The E7 protein encoded by human papillomavirus type 16 is one of the few viral genes that can immortalize primary human cells and thereby override cellular senescence. While it is generally assumed that this property of E7 depends on its interaction with regulators of the cell cycle, we show here that E7 targets insulin-like growth factor binding protein 3 (IGFBP-3), the product of a p53-inducible gene that is overexpressed in senescent cells. IGFBP-3 can suppress cell proliferation and induce apoptosis; we show here that IGFBP-3-mediated apoptosis is inhibited by E7, which binds to IGFBP-3 and triggers its proteolytic cleavage. Two transformation-deficient mutants of E7 failed to inactivate IGFBP-3, suggesting that inactivation of IGFBP-3 may contribute to cell transformation.

Apoptosis↗
PubMed1999

Use of thiophilic adsorption chromatography for the one-step purification of a bacterially produced antibody F(ab) fragment without the need for an affinity tag.

Thiophilic adsorption chromatography (TAC) was employed for the purification of a recombinant F(ab) fragment of the antibody IN-1 from the periplasmic protein fraction of Escherichia coli. Adsorption of the F(ab) fragment to the T-gel was achieved at a high concentration of ammonium sulfate and turned out to be independent of the presence of a His(6) tag or Strep tag or of the human or murine nature of the C(H)1 and C(L) domains (subclass IgG1/kappa). Elution was effected by means of a decreasing salt gradient, yielding fractions with the correctly assembled, heterodimeric F(ab) fragment at high purity. Interestingly, the single substitution of an alanine residue with phenylalanine in the CDR-L1 of the F(ab) fragment significantly enhanced the retention on the column so that quantitative elution necessitated prolonged application of a low-salt buffer. Our findings suggest that TAC is generally suitable for the isolation of bacterially produced F(ab) fragments and support the notion that aromatic side chains play an important role in the interaction with the affinity matrix. This method should prove valuable in the production of proteins for in vivo applications as might be the case for the F(ab) fragment of the antibody IN-1, which promotes axonal regeneration in the central nervous system.

Animals↗
PubMed1998

Randomized, controlled phase II trial of subcutaneous interleukin-2 in combination with highly active antiretroviral therapy (HAART) in HIV patients.

OBJECTIVE: To determine the immunological, virological and clinical effects of subcutaneous IL-2 in 44 HIV-patients in conjunction with pre-existing tri-therapy (zidovudine, 3TC, saquinavir). DESIGN: Partially randomized, controlled, prospective trial. SETTING: Single center study at tertiary care center. PATIENTS: Sixty four patients (CD4 count 200-500 x 10(6)/l). INTERVENTION: Fourty four patients were randomized to receive 5-day cycles of IL-2 (9 Mio IU/d) every 6 weeks (Group A) or whenever the CD4 cell count dropped below the 1.25-fold of baseline (Group B), whereas 20 control patients received the same HAART without IL-2. OUTCOME MEASURES: The optimal individual treatment interval and the immunological and virological effects of subcutaneously administered IL-2 were analysed. Importantly, the level of cellular in vivo immunity and the frequency of dermatological marker diseases and infectious complications were assessed. RESULTS: IL-2 was well tolerated although fever, influenza-like symptoms and indurated injection sites were commonly encountered. After 1 year of IL-2, there was a median increase of more than 100 x 10(6)/l CD4 cells in both IL-2 groups in contrast to the controls (P < 0.01, 0.01 and not significant). The median HIV load did not increase either in plasma or in lymph nodes. Lymphocyte activation decreased as assessed by MHC class II (P < 0.001), CD25 (P < 0.001) and CD38 expression (P < 0.005). Although delayed type hypersensitivity against common recall antigens increased in both IL-2 groups, it did not reach statistical significance. However, it is of note, that in 7 of 11 (63.6%) patients delayed type hypersensitivity against recombinant HIV antigens improved significantly. Whereas there was no opportunistic infection in either IL-2 group, three cases of Kaposi's sarcoma occurred in the controls. Dermatological indicator diseases (thrush, condyloma, herpes simplex) were found to occur more frequently in the control group. CONCLUSIONS: Subcutaneous IL-2 in addition to HAART was safe and led to sustained qualitative and quantitative immunological improvements in the majority of patients. Individualisation of therapy intervals further improved the efficacy and tolerance of IL-2.

Adult↗
PubMed1996

[Periodic paralysis as the first manifestation of hyperthyroidism].

HISTORY AND CLINICAL FINDINGS: A 19-year-old man had mild diarrhoea at the time that suddenly one night he was unable to turn in his bed and the following morning could not move his arms and legs for 4 hours. Neither he nor any family members had previously had any paralysis. Physical examination was unremarkable except for mild tachycardia and first-degree goitre. INVESTIGATIONS: A provocation test with glucose (3 g/kg) and insulin (0.1 IU/kg) caused renewed paralysis for several hours, serum potassium falling from 4.3 to 3.4 mmol/l. The paralysis was reversed on oral potassium (40 mmol) Thyroid function tests revealed hyperthyroidism with an increased concentration of free thyroxine (25.5 pg/ml) and free triiodothyronine (9.7 pg/ml), while thyroid-stimulating hormone was decreased (0.07 mU/I), supporting the diagnosis of autoimmune thyroiditis. TREATMENT AND COURSE: Thyrostatic treatment was started with thiamazole (10 mg every other day). There was no further periodic paralysis and another provocation test was negative. CONCLUSION: Fleeting paralysis is often misdiagnosed as being psychogenic. Potassium abnormalities are the most common cause but are only rarely associated with hyperthyroidism. This case of thyrotoxic hypokalaemic paralysis was probably based on a genetic defect of muscle fibre membrane manifesting itself only in the presence of hyperthyroidism.

Adult↗
PubMed1996

The role of technical, biological and pharmacological factors in the laboratory evaluation of anticonvulsant drugs. VI. Seasonal influences on maximal electroshock and pentylenetetrazol seizure thresholds.

There is strong evidence for circadian rhythmicity in certain seizure types, whereas only a few studies have addressed the possibility of seasonal rhythms in convulsive activity. In the present experiments, seizure thresholds to different types of seizures were determined twice per month over a period of 13 months in mice under controlled environmental conditions, i.e., constant photoperiod, temperature, humidity, and food. Each group of animals was used for only one experiment, and the age of the mice used per month was the same throughout the study. Furthermore, all experiments were done at the same time in the morning to avoid circadian variation. Thresholds for the following seizure types were determined: (1) tonic hindlimb seizures induced by electrical (transauricular) stimulation; (2) myoclonic seizures induced by intravenous (i.v.) infusion of pentylenetetrazol (PTZ); (3) generalized clonic seizures in response to i.v. PTZ; and (4) tonic forelimb seizures induced by PTZ. A significant seasonality was determined for myoclonic and clonic PTZ seizure thresholds with highest thresholds between February and April and lowest thresholds between July and September. No clear seasonality was seen for chemically or electrically induced tonic seizures. Determination of plasma corticosterone did not disclose any seasonal rhythm in adrenal corticosteroid production that resembled the circannual variation in myoclonic and clonic seizure thresholds. In conclusion, our experiments suggest the existence of seasonal rhythms in PTZ seizure thresholds in laboratory animals despite standardized environmental conditions. A possible explanation for the findings may be the known seasonal alteration of the geomagnetic field which, by its effect on the pineal production of melatonin, may act as a seasonal synchronizor ("zeitgeber") in animals in the absence of other synchronizing forces, such as seasonal changes in photoperiod and ambient temperature.

Animals↗
PubMed1995

Texture analysis of the surface of the human skin.

The roughness parameters known from surface engineering often used to describe the microtopography of the surface of the skin do not, by definition, take into account the two-dimensional relationships of the stratum corneum. An approximate description of these relationships can be obtained by scanning several radial profile sections. A more detailed analysis of the characteristic surface relief of the skin can also be based on the texture parameters used to characterize many natural structures. These types of parameters can be extracted from the gray level images of an impression of the surface of the skin--a replica--that has been magnified under a microscope, photographed with a CCD camera and subsequently subjected to image analysis by a digital computer. The purpose of this study is to determine not only the usefulness of texture parameters for describing the morphology of the surface of the human skin but also whether, for example, cosmetically treated skin can be detected by means of texture analysis.

Cosmetics↗
PubMed1991

[A test for the detection of speech and language disorders in the acute phase after stroke. Development and clinical application].

No standardized assessment of aphasic symptoms for stroke patients in the acute phase has as yet been published in the German language. Current test batteries such as the AAT are too time-consuming and cannot be performed on severely impaired patients. A short test for the examination of aphasic and dysarthric symptoms has been developed which contains 7 subtests in three main areas: spontaneous speech, comprehension and planning of movements, speech and language abilities. Since abilities in acute cases may only be functionally impaired and often only detectable after stimulation, standardized stimulation is applied in most of the subtests. In this way it is possible to test acute stroke patients for aphasic and dysarthric symptoms. The course of recovery in a typical case is described.

Aged↗
PubMed1989

Human papillomavirus type 48.

The cloning and partial characterization of the genome of human papillomavirus (HPV) type 48 is presented. Hybridization and short DNA sequence analyses permitted the alignment of the genome to the HPV genetic map.

Carcinoma, Squamous Cell↗
PubMed1985

Review of gunshot wounds in Dayton, Ohio. Demographics, anatomic areas, results, and costs.

A retrospective review of 210 admissions for gunshot wounds was performed to evaluate the frequency that various anatomic areas were injured, complication rates, results of treatment, and costs. Seventy-two percent of patients had a single anatomic site involved. The complication rate was 13% and the death rate was 10.9%. A good result was obtained in 72%, but 12.4% had long-term disabilities. The average length of stay was 11 days with an average cost of +5,682 per patient. Application of today's prospective payment under diagnosis-related groups suggests this system of payment may adversely affect the delivery of trauma care in this country.

Adolescent↗