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Biomedical subjects

G Haase

Publications and source records attributed to G Haase.

At least 73 records · Page 4Linked to original sources
PubMed1998

Adenovirus-mediated transfer of the neurotrophin-3 gene into skeletal muscle of pmn mice: therapeutic effects and mechanisms of action.

Several neurotrophic factors (CNTF, BDNF, IGF-1) have been suggested for the treatment of motor neuron diseases. In ALS patients, however, the repeated subcutaneous injection of these factors as recombinant proteins is complicated by their toxicity or poor bioavailability. We have constructed an adenovirus vector coding for neurotrophin-3 (AdNT-3) allowing for stable and/or targeted delivery of NT-3 to motoneurons. The intramuscular administration of this vector was tested in the mouse mutant pmn (progressive motor neuronopathy). AdNT-3-treated pmn mice showed prolonged lifespan, improved neuromuscular function, reduced motor axonal degeneration and efficient reinnervation of muscle fibres. NT-3 protein and also adenovirus vectors, when injected into muscle, can be transported by motoneurons via retrograde axonal transport to their cell bodies in the spinal cord. Using ELISA and RT-PCR analyses in muscle, spinal cord and serum of AdNT-3-treated pmn mice, we have investigated the contribution of these processes to the observed therapeutic effects. Our results suggest that most if not all therapeutic benefit was due to the continuous systemic liberation of adenoviral NT-3. Therefore, viral gene therapy vectors auch as adenoviruses, AAVs, lentiviruses and new types of gene transfer not based on viral vectors that allow for efficient in vivo liberation of neurotrophic factors have potential for the future treatment of human motor neuron diseases.

Adenoviridae↗
PubMed1998

The rationale and method for constructing internal control DNA used in pertussis polymerase chain reaction.

The inclusion of an appropriate internal control DNA in polymerase chain reaction (PCR) is a rapid and simple method for the detection of PCR failure. Two PCR coamplification internal control DNAs (ICD I and ICD II) with the same primer-binding sequences as the target DNA for the detection of Bordetella pertussis and Bordetella parapertussis were produced using an overlap extension technique and a PCR MIMIC construction kit, respectively. The ICD II was further evaluated in a prospective clinical study in 360 patients with a clinical diagnosis of pertussis. From 360 nasopharyngeal swabs the internal control was positive in 318 (88%) samples, but was negative in 42 (12%). After phenol-chloroform extraction an additional 10 internal controls became positive. For the detection of PCR failure, the use of internal control DNA is highly recommended for PCR-based identification of B. pertussis and B. parapertussis organisms from nasopharyngeal swabs and aspirates.

Bordetella↗
PubMed1998

Effect of duration of treatment on treatment outcome and cost of treatment for Wilms' tumor: a report from the National Wilms' Tumor Study Group.

PURPOSE: National Wilms' Tumor Study (NWTS)-4 was designed to evaluate the efficacy, toxicity, and cost of the administration of different regimens for the treatment of Wilms' tumor (WT). PATIENTS AND METHODS: Between August 6, 1986 and September 1, 1994, 905 previously untreated children aged younger than 16 years with stage II favorable histology (FH) WT (low-risk [LR]), stages III to IV FH WT, or stages I to IV clear-cell sarcoma of the kidney (high-risk[HR]) were randomized after the completion of 6 months of chemotherapy to discontinue (short) or continue for 9 additional months (long) treatment with chemotherapy regimens that included vincristine and either divided-dose (standard [STD]) courses (5 days) or single-dose (pulse-intensive [PI]) treatment with dactinomycin. HR patients also received either divided-dose (STD) courses (3 days) or single-dose (PI) treatment with doxorubicin. RESULTS: The 4-year relapse-free survival (RFS) rates after the second randomization for LR patients were 83.7% for the 190 patients treated with short and 88.2% for the 187 patients treated with long chemotherapy (P = .11). The 4-year RFS rates after the second randomization for HR FH patients were 89.7% for the 256 patients treated with short and 88.8% for the 246 patients treated with long chemotherapy (P = .87). The charge for treatment with the short PI treatment regimens for all children with stages I through IV FH WT was approximately one half of that with the long STD treatment regimens. CONCLUSION: The short administration schedule for the treatment of children with WT is no less effective than the long administration schedule and can be administered at a substantially lower total treatment cost.

Adolescent↗
PubMed1998

Exophiala dermatitidis and Sarcinomyces phaeomuriformis: ITS1-sequencing and nutritional physiology.

The internal transcribed spacer 1 (ITS1) sequences of the nuclear rRNA gene (approximately 200 bp) of 33 strains of the Exophiala dermatitidis complex were determined; two similar species were added for comparison. A core group (I), including the type strain CBS 207. 35, contained 20 identical strains which had previously been found to have introns in their small sub-unit (SSU) rDNA. Eleven remaining strains identified as E. dermatitidis (groups II-V) differed from the core group in 1-4 nucleotide positions (plus a deletion in one strain); most of them lacked introns in their SSU ribosomal genes. The type strain of the meristematic species Sarcinomyces phaeomuriformis CBS 131.88 was found to differ significantly from E. dermatitidis. One strain had the annellidic morphology of E. dermatitidis, but the ITS1 sequence of S. phaeomuriformis. Strain CBS 709.95, an E. dermatitidis reported to have a meristematic synanamorph, was found to have ITS1 identity to the type strain of E. dermatitidis, although SSU sequences established previously suggested a close relationship with S. phaeomuriformis. Slight physiological differences were found between E. dermatitidis and S. phaeomuriformis. An oligonucleotide probe specific for E. dermatitidis was designed, thus able to discriminate this species from closely related black yeasts.

Base Sequence↗
PubMed1998

Molecular phylogeny and taxonomy of medically important fungi.

Some recent advances in study of molecular evolution and taxonomy of human pathogens are discussed. In systemic Onygenales as well as in Chaetothyriales, pathogenic species are phylogenetically intermingled with non-pathogenic taxa. When a teleomorph of Coccidioides immitis is eventually found, it is predicted to resemble Uncinocarpus, a genus otherwise comprising environmental species. In the dermatophytes, Trichophyton and Microsporum are paraphyletic, whereas Epidermophyton is polyphyletic. On the basis of 18S and ITS rDNA sequencing data, Exophiala anamorphs (black yeasts) are confirmed to be closely related to the ascomycete genus Capronia. The related neurotropic species Cladophialophora bantiana is remarkable in consistently having introns in its 18S rDNA gene.

Animals↗
PubMed1997

Phenotypic alteration of astrocytes induced by ciliary neurotrophic factor in the intact adult brain, As revealed by adenovirus-mediated gene transfer.

Synthesis of the ciliary neurotrophic factor (CNTF) and its specific receptor (CNTFRalpha) is widespread in the intact CNS, but potential biological roles for this system remain elusive. Contradictory results have been obtained concerning a possible effect on the morphological and biochemical phenotype of astrocytes. To reassess this question, we have taken advantage of adenovirus-mediated gene transfer into the rat brain to obtain the local release of CNTF. Stereotaxic administration of CNTF recombinant adenovirus vectors into the striatum led to phenotypic changes in astrocytes located in regions that were related axonally to striatal neurons at the injection site. Astrocytes appeared hypertrophied and displayed an increase in both GFAP and CNTF immunoreactivity. This response was observed up to 5 weeks after injection, the longest time studied. It was not observed after the administration of a control vector. The methodology used in the present study, allowing us to analyze the effect of the factor in areas remote from the injection site, has provided conclusive evidence that CNTF affects the astroglial phenotype in the intact CNS. The characteristics of these effects may explain why contradictory results have been obtained previously, because this signaling system seems to have a low efficiency and therefore requires a high local concentration of the factor close to the target cells. One might speculate as to the involvement of a CNTF astroglio-astroglial signaling system in the organized response of a population of astrocytes to changes in CNS homeostasis detected locally, even by a single cell.

Adenoviridae↗
PubMed1997

Coniosporium perforans and C. apollinis, two new rock-inhabiting fungi isolated from marble in the Sanctuary of Delos (Cyclades, Greece).

Coniosporium perforans and C. apollinis, originating from marble in the Mediterranean basin, are described as new species of rock inhabiting microcolonial fungi. The morphologically similar species Monodictys castaneae (Wallr.) S. Hughes, Phaeosclera dematioides Sigler et al., and a Coniosporium-like strain are compared using 18S rDNA phylogeny and Restriction Length Fragment Polymorphism analysis of Internal Transcribed Spacer regions. Sarcinomyces crustaceus Lindner is additionally compared on the basis of 18S rDNA sequencing data. Phylogenetic analysis suggests that Phaeosclera dematioides is related to the ascomycetous order Dothideales and Monodictys castaneae to the Pleosporales, whereas the three Coniosporium species studied are a sister group to the Herpotrichiellaceae (Chaetothyriales). A similar affinity was suggested previously for the recently described meristematic rock-fungus Sarcinomyces petricola Wollenzien & de Hoog. Sarcinomyces crustaceus appears unrelated to this group, and hence the present new taxa cannot be described in this genus.

Base Sequence↗
PubMed1997

Gene therapy of murine motor neuron disease using adenoviral vectors for neurotrophic factors.

Motor neuron diseases such as amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy cause progressive paralysis, often leading to premature death. Neurotrophic factors have been suggested as therapeutic agents for motor neuron diseases, but their clinical use as injected recombinant protein was limited by toxicity and/or poor bioavailability. We demonstrate here that adenovirus-mediated gene transfer of neurotrophin-3 (NT-3) can produce substantial therapeutic effects in the mouse mutant pmn (progressive motor neuronopathy). After intramuscular injection of the NT-3 adenoviral vector, pmn mice showed a 50% increase in life span, reduced loss of motor axons and improved neuromuscular function as assessed by electromyography. These results were further improved by coinjecting an adenoviral vector coding for ciliary neurotrophic factor. Therefore, adenovirus-mediated gene transfer of neurotrophic factors offers new prospects for the treatment of motor neuron diseases.

Adenoviridae↗
PubMed1997

Endophthalmitis due to Microbacterium species: case report and review of microbacterium infections.

Microbacterium species (formerly CDC [Centers for Disease Control and Prevention] coryneform group A-4 and A-5 bacteria) are widely distributed in the environment and rarely cause infections in humans. We present a case of endophthalmitis due to Microbacterium species that occurred after accidental trauma and review the literature on microbacterium infections. If the infected tissue or medical device is removed and antimicrobial therapy (preferably with beta-lactams or glycopeptides) is instituted, the prognosis is usually favorable for patients with microbacterium infections.

Adult↗
PubMed1996

[Lemierre's post-tonsillitis sepsis with meningitis and intravascular consumption coagulopathy as complication of infectious mononucleosis with pansinusitis].

HISTORY AND CLINICAL FINDINGS: 24 days after the onset of infectious mononucleosis, clinically and serologically confirmed, an otherwise healthy 18-year-old schoolboy developed a fulminant septicaemia with acute meningitis and loss of consciousness, consumptive coagulopathy and acute renal failure. INVESTIGATIONS: Computed tomography demonstrated pansinusitis. Lumbar puncture produced purulent cerebrospinal fluid with 11,500 cells/microliters, predominantly granulocytes, protein 205 mg/dl, glucose 19 mg/dl, indicating bacterial meningitis. The suspected diagnosis of posttonsillitis septicaemia (Lemierre's syndrome) was confirmed by repeated demonstration of fusiform gram-negative bacteria in anaerobic blood cultures, identified as Fusobacterium necrophorum. Anaerobic CSF culture grew Prevotella bivia of the Bacteroidaceae family. TREATMENT AND COURSE: Both the consumptive coagulopathy and the renal failure were successfully treated and the patient's condition stabilized. The sinuses were surgically drained under high doses of piperacillin/sulbactam and chloramphenicol. Despite the sensitivity of the cultured bacteria to the administered antibiotics the septic temperature continued, but disappeared within 4 days of metronidazole having been added. After 5 weeks of antibiotic treatment, three of them in an intensive care unit, the patient was discharged in good general condition. CONCLUSION: This case illustrates that severe septicaemia caused by rare bacteria may follow an attack of infectious mononucleosis which had taken an uncomplicated course.

Acute Kidney Injury↗
PubMed1996

Renal failure in Wilms' tumor patients: a report from the National Wilms' Tumor Study Group.

This report defines the incidence and determines the etiology of renal failure (RF) in patients undergoing treatment for Wilms' tumor (WT). The database of the National Wilms' Tumor Study (NWTS) was searched to identify all children reported to have developed chronic renal failure. There were 55 patients found to have RF. Of these, 39 patients had bilateral tumors, 15 with unilateral disease and one with a WT in a solitary kidney. The median interval from diagnosis to the onset of renal failure was 21 months. The incidence of RF in bilateral WT was 16.4% for NWTS-1 & -2, 9.9% for NWTS-3, and 3.8% for NWTS-4. The incidence of RF in unilateral WT remained stable. The most common etiologies of RF were: bilateral nephrectomy for persistent or recurrent tumor (24 pts), Drash syndrome (12 pts), progressive tumor in the remaining kidney (5 pts), radiation nephritis (6 pts), and other causes (5 pts). The etiology of renal failure was not reported in three children. Children with unilateral WT and a normal contralateral kidney have a very low incidence of RF, and this review does not support a recommendation for parenchymal sparing procedures in these patients. Children with bilateral WT are at risk for the development of RF, and parenchymal sparing procedures are warranted.

Child↗
PubMed1996

Renal salvage procedures in patients with synchronous bilateral Wilms' tumors: a report from the National Wilms' Tumor Study Group.

Synchronous bilateral Wilms' tumor accounts for 4% to 6% of all Wilms' tumors. Renal salvage procedures (partial nephrectomy and enucleation) have been recommended to conserve renal parenchyma. The objective of this study was to review the results of renal salvage operations performed in children who had bilateral neoplasms. The authors reviewed the records of 98 children enrolled in the Fourth National Wilms' Tumor Study who had synchronous bilateral tumors and underwent renal salvage procedures. One hundred thirty-four kidneys were managed with renal salvage procedures. Complete excision of gross disease was accomplished in 118 (88%) of the 134 kidneys. Local tumor recurrence in the remnant kidney or tumor bed occurred in 11 cases (8.2%). Overall, 72% of the kidneys were preserved, and the 4-year survival rate was 81.7%. The surgical morbidity after a salvage procedure was comparable to that of a complete nephrectomy in patients with unilateral Wilms' tumor. Although the incidence of positive surgical margins is worrisome, it did not invariably lead to local recurrence in the remnant kidney or the tumor bed.

Biopsy↗