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M Baumann

Publications and source records attributed to M Baumann.

At least 55 records · Page 3Linked to original sources
PubMed2001

Combinatorial synthesis of cholesterol ester transfer protein-mRNA ligands and screening by nondenaturating gel-electrophoresis.

RNA, as one of the biomolecules with the most structural and functional diversity, is an attractive therapeutic target.(1) Employing combinatorial chemistry methods, small peptide ligands were found, which bind to a short RNA with important biological functions. A 23-nt RNA oligonucleotide from the cholesterol ester transfer protein mRNA was chosen as a molecular target.(2) A 27-nt RNA oligonucleotide from the human immunodeficiency virus type-1 (HIV-1) TAR RNA was used to control the binding specificity.(3) Tetrapeptide libraries, composed of the amino acids Lys, Tyr, Leu, Ile, and Arg, with and without C- and N-terminal lysines, were synthesized by a combination of combinatorial and divergent solid-phase synthesis. Gel-shift affinity screening was used to extract the peptides with the best RNA binding properties. The peptide Lys-Tyr-Lys-Leu-Tyr-Lys-Cys-NH(2) (1) showing micromolar affinity to its RNA target was characterized with circular dichroism (CD), ultra violet (UV) measurement, and (1)H NMR spectroscopy.

5' Untranslated Regions↗
PubMed2001

Unusual features of long-range density fluctuations in glass-forming organic liquids: a Rayleigh and Rayleigh-Brillouin light scattering study.

A new feature of glass-forming liquids, i.e., long-range density fluctuations of the order of 100 nm, has been extensively characterized by means of static light scattering, photon correlation spectroscopy and Rayleigh-Brillouin spectroscopy in orthoterphenyl (OTP) and 1,1-di(4(')-methoxy-5(')methyl-phenyl)-cyclohexane (BMMPC). These long-range density fluctuations result in the following unusual features observed in a light scattering experiment, which are not described by the existing theories: (i) strong q-dependent isotropic excess Rayleigh intensity, (ii) additional slow component in the polarized photon correlation function, and (iii) high Landau-Placzek ratio. These unusual features are equilibrium properties of the glass-forming liquids and depend only on temperature, provided that the sample has been equilibrated long enough. The temperature-dependent equilibration times were measured for BMMPC and are about 11 orders of magnitude longer than the alpha process. It was found that the glass-forming liquid OTP may occur in two states: with and without long-range density fluctuations ("clusters"). We have characterized the two states by static and dynamic light scattering in the temperature range from T(g) to T(g)+200 K. The relaxation times of the alpha process as well as the parameters of the Brillouin line are identical in both OTP with and without clusters. The alpha process (density fluctuations) in OTP was characterized by measuring either the polarized (VV) or depolarized (VH) correlation function, which are practically identical and q-independent. This feature, which is commonly observed in glass-forming liquids, is not fully explained by the existing theories.

Journal Article↗
PubMed2001

Rat model of lung fibrosis: comparison of functional, biochemical, and histopathological changes 4 months after single irradiation of the right hemithorax.

This study investigated changes in lung function, hydroxyproline (OH-pro) content of lung tissue and histopathology in anesthetized, spontaneously breathing rats after a single, selective irradiation of the right hemithorax with a single dose of 20 Gy. The objective of this animal model was to examine as to whether non-invasive lung function measurements (LFM) could be used to analyze the magnitude of the irradiation-related pneumonitis and its long-term sequel occurring in the right lung in the presence of a normal left lung. Four months after irradiation, the OH-pro content in the irradiated right lung was determined and compared with the non-irradiated contralateral left lung, as well as lungs from non-irradiated sham controls. LFM revealed significantly depressed flow-volume curves and reduced quasistatic compliance, suggesting a marked diminution of elastic recoil of the lung. Total lung capacity (TLC) was significantly decreased, while the residual volume (RV) and functional residual capacity (FRC) remained almost unchanged. One of the most predominant dysfunction of the lung was a severe maldistribution of ventilation shown by the single-breath N(2)-wash-out test. Single-breath carbon monoxide diffusing capacity (Dlco) was significantly decreased. The content of OH-pro, a marker of increased collagen, was significantly increased in the irradiated right lung but was indistinguishable from sham controls in the non-irradiated left lung. Histopathological examinations provided evidence of both inflammatory and fibrotic lesions in the irradiated lobes, including bronchiolo-alveolar hyperplasia. No changes were observed in the non-irradiated left lung. In summary, effects observed in the irradiated right lung were largely consistent with effects described in other animal models of human interstitial pulmonary fibrosis. Non-invasive LFM were considered to be particularly sensitive to study the overall extent of changes, however, the interpretation of findings appears to be complicated by the lobar heterogeneity of tissue- and flow-related functional end points.

Airway Resistance↗
PubMed2001

The translational research chain: is it delivering the goods?

PURPOSE: To address whether the translational research chain has influenced clinical practice in radiation oncology. METHODS AND MATERIALS: Merits and limitations of the various steps of the translational chain, i.e., in vitro studies, animal experiments, biomathematical modeling, Phase I and II trials, and randomized Phase III trials are briefly reviewed. The process and value of translational research in radiation oncology are addressed using dose fractionation and the time factor in tumors as examples. RESULTS: The examples show that translational research may indeed change clinical practice in radiation oncology. However, it takes several decades and considerable efforts to define and test new strategies. The "translational process" is by no means unidirectional but a continuing multiway dialog among basic scientists, applied scientists, clinical scientists, and clinical oncologists. CONCLUSION: Translational research works in radiation oncology, and it is difficult to conceive a better alternative for future improvement of therapy. The slow speed of the translational process indicates that there is a need for improving the various steps of the translational network and the interaction as a whole. Massive investments in one part of the network are likely to be at least partly wasted unless the other links are strengthened as well.

Animals↗
PubMed2001

The results of colorectal cancer treatment by p53 status: treatment-specific overview.

PURPOSE: Both negative and positive influences of mutant p53 on treatment outcome have been reported, and we present here a meta-analysis of published studies where outcome was reported for defined treatment groups. METHODS: We identified articles on the effect of p53 status by treatment modality, excluding those not stratified by method of treatment. A common hazard ratio was estimated from studies that reported a multivariate analysis. We also estimated the numbers of patients expressing the endpoint at the mean or median follow-up time and calculated a pooled odds ratio. RESULTS: Twenty-eight articles were evaluable (23 using immunohistochemistry to detect overexpression of p53 and 8 using DNA sequencing), for a total of 4,416 patients. For patients treated with surgery only, the immunohistochemistry studies showed a significant influence of p53 status on disease-free survival and a marginally significant influence on overall survival. In the studies using DNA sequencing, by contrast, there was a significant influence of p53 mutations on overall survival, but not disease-free survival. For patients treated with surgery and radiotherapy, the influence of p53 status on disease-free survival was either insignificant or marginally significant, depending on test used; there was no influence on overall survival. CONCLUSIONS: Although this pooled analysis of published studies where treatment was accounted for shows that there is a borderline significant hazard associated with p53 overexpression or mutation vs. p53 wild-type, it is unlikely that p53 can be applied in a routine clinical setting alongside factors such as T stage, nodal status, and residual tumor, whose prognostic value is much stronger.

Adenocarcinoma↗
PubMed2001

Autologous peripheral blood stem cell transplantation and anti-B-cell directed immunotherapy for refractory auto-immune haemolytic anaemia.

UNLABELLED: We report the clinical course of a 6.5-year-old boy with refractory auto-immune haemolytic anaemia. Due to failure of conventional immunosuppressive therapy, an autologous peripheral blood stem cell transplantation was performed. The conditioning regimen consisted of cyclophosphamide and anti-thymocyte globulin. The patient was reinfused with 2.6 x 10(6) CD34 positive selected, B- and T-cell-depleted peripheral blood stem cells per kg body weight. He showed a partial response with a reduced demand for red blood cell transfusions. However, due to persistence of the haemolytic process he was started on rituximab therapy on day +40 post-transplant. Following two doses of rituximab, the patient improved rapidly and developed a sustained complete response. After 10 months, haemolysis recurred and responded again to rituximab therapy without the necessity for red blood cell transfusions. 15 months after initial antibody treatment, however, the patient developed a second relapse which was now refractory to rituximab therapy although CD20+ B-lymphocytes were cleared from the peripheral blood. CONCLUSION: Our case report suggests that rituximab and autologous peripheral blood stem cell transplantation are important though not curative elements in the treatment of patients with severe auto-immune haemolytic anaemia who are refractory to conventional immunosuppressive therapy.

Anemia, Hemolytic, Autoimmune↗
PubMed2001

No evidence for a different magnitude of the time factor for continuously fractionated irradiation and protocols including gaps in two human squamous cell carcinoma in nude mice.

BACKGROUND AND PURPOSE: To study whether the magnitude of the time factor is different for continuously fractionated irradiation and for fractionation protocols including gaps. MATERIALS AND METHODS: Two human head and neck squamous cell carcinomas (SCCs), FaDu and GL, were transplanted subcutaneously into the right hindleg of NMRI (nu/nu) mice and irradiated with 30 fractions under ambient conditions within 2, 6 and 10 weeks. Irradiations within 6 and 10 weeks were given either as a continuous course or with a mid-course gap of 3 weeks. The end-point of the experiments was local tumor control at day 120 (FaDu) or day 180 (GL) after the end of treatment. RESULTS: In FaDu tumors, two experimental cohorts (A, B) yielded significantly different results and were analyzed separately. In cohort A, the tumor control dose 50% (TCD50) increased from 37 to 89 Gy when the treatment time of continuous fractionated irradiation was extended from 2 to 10 weeks. The recovered dose/day (D(r)) was 0.98 Gy (95% confidence interval, 0.72; 1.27). In cohort B, the TCD50 increased from 35 to 63 Gy, and the D(r) was 0.51 Gy (0.24; 0.75). In GL tumors, the TCD50 for continuously fractionated irradiation increased from 41 to 48 Gy. This increase was not significant, and the D(r) was 0.15 Gy (0; 0.30). None of the TCD50 and D(r) values obtained in both tumor models for continuous irradiation vs. irradiation with a gap were significantly different. CONCLUSIONS: Prolongation of the overall treatment time of fractionated irradiation resulted in a pronounced decrease of local control in human FaDu SCC and little decrease of local control in human GL SCC. No evidence was found that the magnitude of the time factor in these tumors is different for continuous fractionation or fractionation protocols including gaps.

Animals↗
PubMed2001

Predictive factors in radiotherapy for non-small cell lung cancer: present status.

PURPOSE: To evaluate the predictive factors for radiation response in non-small cell lung cancer (NSCLC) and the role of such factors in guiding high dose radiation therapy. METHODS: The first International Workshop on Prognostic and Predictive Factors in Lung Cancer was organized by the Hellenic Cooperative Oncology Group and held in Athens, Greece under the auspices of the International Association for the Study of Lung Cancer. Presentations at this meeting provided the outline of this report, which has also been supplemented with available data from the current literature. RESULTS: The predictive factors for both the natural history and the therapy outcome of NSCLC are grouped as follows: (1) tumor related factors (anatomic factors); the extent of tumor (tumor stage) is one of most important prognostic factors affecting the therapy outcome. Tumor size (T stage), anatomical structures involved (T4 vs. T3 lesion), and the presence of regional lymph node metastasis have a significant impact on both prognosis and response to appropriate therapy; (2) host-related factors (clinical factors) that are important in therapy response include performance status, weight loss of more than 10% of body weight in the previous 6 months, and associated co-morbidities, i.e. pulmonary and cardiac diseases; (3) technical factors of radiation therapy which play a decisive role in successful outcome. The target volume should be defined accurately using modern imaging studies. The radiation dose fractionation schedule, in terms of the dose intensity and total dose, should be high enough to provide local tumor control in the majority of patients. Three-dimensional (3-D) conformal planning is an essential tool in dose escalation studies to determine the maximum tolerated dose of radiation; (4) biological/radiobiological/metabolic factors. Biologic markers resulting from genetic lesions in lung cancer are grouped as follows: (a) oncogene amplification and overexpression (aberrant gene expression) and mutated tumor suppressor genes -- ras gene, myc gene, HER-2/neu and survivin gene, p53 and mutated beta-tubulin gene; (b) tumor biologic/radiobiologic factors -- tumor cell proliferation kinetics, hypoxia, intrinsic cellular radiosensitivity, gamma factor, and DNA content; (c) enzymes and hormones: neuron-specific enolase, serum lactate dehydrogenase, and enhanced glucose metabolic rate supported by increased glucose transporter protein. The surviving fraction of tumor cells at 2.0 Gy of radiation (SF2) as a measure of intrinsic tumor cell radiosensitivity, potential doubling time (T(Pot)) as a measure of the rate of tumor cell proliferation and gamma factor representing the slope of the survival curve at 50% survival rate are being investigated as potential predictors for therapy response. Enhanced glucose utilization, a hallmark of malignant transformation, is being studied as a potential monitor for therapy response by using PET-FDG. CONCLUSION: Current data indicate that there is a dose-response relationship between radiation dose and local tumor control, and also between local tumor control and survival in stage III NSCLC. Therapeutic factors, i.e. total radiation dose, fractionation schedule and dose intensity, and use of 3-D conformal radiation to secure the optimum therapeutic ratio are important for improved local tumor control and survival. Future research should be directed towards radiation dose escalation using 3-D conformal therapy to determine the maximum tolerated dose (MTD) of radiation in chemo-radiotherapy, and the use of this MTD for improved local tumor control and survival. Radiobiological, molecular, and metabolic markers may have potential for monitoring tumor response and optimizing radiation therapy.

Biomarkers, Tumor↗
PubMed2001

Dose and fractionation concepts in the primary radiotherapy of non-small cell lung cancer.

At present, radiotherapy alone or in combination with chemotherapy offers the only chance of cure of medically inoperable or locally advanced unresectable non-small cell lung cancer. The radiobiological basis and clinical results of current dose and fractionation concepts in the primary radiotherapy of NSCLC are briefly reviewed. Whenever possible, focus is given to the results of randomized phase III trials. With the exception of early disease treated to doses higher than 60 Gy, the prognosis of inoperable localized NSCLC is very poor. Local recurrence is the major cause of failure after radiation therapy calling for intensified local treatment. Dose-escalation using conventional fractionation or moderate hypofractionation is promising but randomized trials are presently not available. Dose-escalated hyperfractionation theoretically offers advantages, however, there appears currently no strong evidence from randomized trials supporting this approach in NSCLC. The highly accelerated CHART regimen significantly improved survival by 9% compared to standard radiotherapy. Nevertheless, even when treated with CHART, about 80% of all patients will eventually develop local recurrence and 60% distant metastases. Many trials on combined radiochemotherapy have used radiotherapy regimens that are not optimal from a current perspective. Because of the high rate of both, local recurrence and distant metastases, future research should be directed to further intensify radiotherapy as well as to integrate such protocols with systemic treatment in carefully selected patients. Since toxicity is expected to increase, state-of-the-art 3D conformal radiation techniques need to be part of clinical trials testing such strategies.

Carcinoma, Non-Small-Cell Lung↗
PubMed2001

Therapy of localized non-small cell lung cancer (take home messages).

Surgery remains the mainstay in curative therapy of stage I and II NSCLC and selected patients with stage III disease. The high rate of distant metastases occurring in patients after complete surgical resection demonstrates the need for effective adjuvant systemic therapy. However, outside of trials, (neo)adjuvant chemotherapy is currently not considered as an established standard in localized NSCLC. Postoperative radiotherapy increases local tumor control in completely resected N2 disease and after R1/R2 resections and is generally recommended in these situations. In inoperable patients radiotherapy offers the only chance of cure. Combined radiochemotherapy and the highly accelerated CHART radiotherapy have been shown to be superior to standard radiotherapy. Progress in the treatment of localized NSCLC over the last decades has been only modest and with the exception of favourable subgroups, prognosis of NSCLC remains grim. In the light of the high rate of local and distant metastases multidisciplinary approaches appear necessary in the vast majority of patients.

Antineoplastic Agents↗
PubMed2001

Standardized ultrasound as a new method to induce platelet aggregation: evaluation, influence of lipoproteins and of glycoprotein IIb/IIIa antagonist tirofiban.

Most of the published studies concerning platelet aggregation were performed with chemical stimulation procedures, however, mechanical stimulation might be a better simulation of physiological activation of platelets. In order to evaluate the influence of ultrasound on platelet aggregation in vitro, we developed an ultrasound device in a standardized set-up, and we evaluated the influence of lipoproteins and the glycoprotein IIb/IIIa inhibitor tirofiban on ultrasound induced platelet aggregation. A cylindrical shaped plastic test tube with 1 ml of platelet-rich plasma was placed in an ultrasound bath (35 kHz) for 5 s. The ultrasound energy transfer into the sample (Delta W=3.77 J) was calculated using the average temperature increase (averaged by 0.935 degrees C) of the sample. Platelet aggregation was quantified immediately after stimulation with ultrasound or adenosine diphosphate (ADP 2.1 and 4.2 microM) by the Myrenne Aggregometer PA2 at low (40 s(-1)) and afterwards at high (2500 s(-1)) shear. To evaluate the influence of lipoproteins, seven healthy male volunteers were investigated before and after a fat load (50 g fat per m(2) body surface), and 11 patients suffering from hypercholesterolemia and atherosclerotic disease before and after a single low-density lipoprotein (LDL) apheresis. Platelet aggregation after ultrasound stimulation was well correlated with platelet aggregation after ADP (r between 0.50 and 0.95). However, when exposed to high shear, the low shear-induced platelet aggregates were more stable after ultrasound stimulation compared with ADP stimulation either with or without tirofiban. After the fat load triglyceride concentration increased from 0.86+/-0.39 to 2.10+/-1.10 mmol l(-1) (P<0.05) resulting in a reduced formation of platelet aggregates after weak (ADP 2.1 microM) but not after strong (ADP 4.2 microM or ultrasound) stimuli. After a single LDL apheresis LDL cholesterol dropped from 3.99+/-0.90 to 1.06+/-0.55 mmol l(-1) (P<0.005). No changes in platelet aggregation were observed with the exception of a lower aggregation when exposed to high shear after stimulation with 2.1 microM ADP. In conclusion, we found the ultrasound stimulation of platelet-rich plasma easy to perform. The platelet aggregation after ultrasound stimulation correlated well with stimulation after ADP. While a reduction in LDL cholesterol concentration had only slight effects on platelet aggregation, an increase in triglyceride concentration resulted in a reduced formation of platelet aggregates after weak stimulation.

Blood Platelets↗
PubMed2001

Proteomics: posttranslational modifications, immune responses and current analytical tools.

The publication of the human genome sequence enables most of the still unknown protein sequences to be added to the current databases. A sequence alone does not, however, give information about the possible expression level of the corresponding protein, neither does it inform about the possible posttranslational modifications, like phosphorylation, glycosylation or changes in individual amino acids. Thus, the human proteome project, a large scale analysis of the functions of gene products, will have an enormous impact on our understanding of the biochemistry of proteins, processes and pathways they are involved in. The diversity in proteins is considerably expanded by various posttranslational modifications. These also pose problems to the investigators, but their careful analysis often pays back because they can reveal important properties in proteins or peptides--like an increased antigenicity leading to (auto)immune responses or an active form of a signaling protein. Immune tolerance usually exists towards self-proteins, but in specific cases it may be broken by posttranslational modifications in the proteins. Novel mass spectrometric, affinity and display techniques offer valuable tools for the large-scale analysis of proteomes. In the present paper we discuss their use for the detection of posttranslational modifications, functional interactions and possible disease-associated abnormalities in proteins.

Electrophoresis, Gel, Two-Dimensional↗
PubMed2001

[Contact litholysis of gallstones with methyl tert-butyl ether in risk patients--a case report].

INTRODUCTION: Before laparoscopic cholecystectomy and endoscopic therapy became gold standard the nonsurgical treatment of symptomatic cholelithiasis, i.e. contact dissolution using methyl-tert-butyl ether (MTBE), was a valuable alternative. Even nowadays, stone dissolution may be helpful in critically ill patients. CASE REPORT: A 85-year-old man admitted in poor general condition due to cholangitis with septicemia following endoscopic retrograde cholangiopancreatography (ERCP) with papillotomy and partial stone removement because of impending perforation of the gallbladder empyema was treated by a percutaneous cholecystostomy with a pigtail catheter. After clinical improvement a successful contact dissolution was initiated by irrigation of the common bile duct and gallbladder with MTBE. The patient is asymptomatic three months after treatment. DISCUSSION: Symptomatic cholelithiasis is usually treated by endoscopic techniques. Percutaneous cholecystostomy in association with contact litholysis using MTBE is an effective treatment in patients who can not be operated due to critical conditions. The success rate in case of cholesterol stones averages 70 to 95% depending on number and size of stones. It is a non-invasive treatment with few side effects. CONCLUSION: In high-risk patients with severe cholecystitis, percutaneous catheter cholecystostomy combined with contact litholysis using MTBE is a successful, safe, and cheap treatment.

Aged↗
PubMed2001

Efficacy and safety of an intravenous monoclonal anti-HBs in chronic hepatitis B patients.

BACKGROUND/AIMS: In this study the safety and efficacy of a monoclonal anti-HBs, Tuvirumab (Mab), were investigated. Tuvirumab is a human monoclonal antibody recognizing the stable 'a'-determinant of the HBsAg. METHODS: We included ten chronic hepatitis B patients: four received monotherapy, and six combination therapy with interferon alpha 2b. RESULTS: Because the development of insoluble [HBsAg-HBsAb] complexes led to adverse events, the Mab dose had to be reduced in seven patients. In nine patients treatment was stopped prematurely because of lack of efficacy, i.e. neutralization of HBsAg in serum. However, temporary HBsAg levels were reduced by at least 50% in all patients; in three patients receiving combination therapy, background levels of HBsAg in serum were reached. A loss of serum HBV-DNA was seen in three patients in the combination group, followed by HBeAg seroconversion in two patients. CONCLUSIONS: We conclude that Mab was not effective in achieving primary efficacy as assessed by neutralization of circulating HBsAg. Whether a combination of Mab with an antiviral agent that reduces the HBsAg load--and therefore minimizes the risk of adverse events--may result in clinical efficacy should be investigated.

Adult↗
PubMed2001

Modulation of ara-CTP levels by fludarabine and hydroxyurea in leukemic cells.

The rate of ara-cytosine triphosphate (ara-CTP) accumulation and its retention has been correlated with 1-beta-D-arabinofuranosylcytosine (ara-C)-mediated toxicity and clinical outcome in childhood and adult leukemia. We tested to what extent preincubation with the ribonucleotide reductase inhibitors fludarabine (F-ara-A) and hydroxyurea (HU) enhanced ara-CTP levels in two human myeloid (HL-60, CMK) and two lymphoblastic leukemia cell lines (MOLT-4, BLIN-1) and also in blasts from 28 children with acute leukemia (AML: 14, ALL: 14). Incubation experiments carried out with cell lines showed F-ara-A and HU to be equipotent in increasing ara-CTP levels. The highest increase was observed in HL-60 cells whereas preincubation had no modulatory effect in MOLT-4 cells. Accordingly, modulation of intracellular ara-CTP levels differed between the subtypes of childhood acute leukemia: whereas in T-ALL (five) preincubation with F-ara-A and HU had no effect on intracellular ara-C metabolism, increased ara-CTP levels were seen in some cases of pre-B-ALL (seven). In myelogenous blasts (12) clinically relevant enhancement of ara-C toxification was regularly obtained with both, F-ara-A (1.9-fold) and HU (1.5-fold). In conclusion, our data suggest that combinations of ara-C and ribonucleotide reductase inhibitors are apt to increase ara-CTP levels depending on the individual cell type and its sensitivity towards ara-C modulators.

Adult↗
PubMed2001

Prediction of progressive liver fibrosis in hepatitis C infection by serum and tissue levels of transforming growth factor-beta.

Although many patients with chronic viral hepatitis C infection suffer from progressive liver disease, the rate of fibrosis progression is highly variable and some patients do not show any measurable progression. However, our ability to predict which patients progress is very limited. Since transforming growth factor-beta (TGF-beta) is a key mediator of liver fibrogenesis, we assessed the predictive role of TGF-beta for fibrogenesis in chronic hepatitis C. We studied 39 patients with chronic hepatitis C in whom two liver biopsies were taken at least 12 months apart, and who did not receive therapy during this period. TGF-beta was measured by bioassay and by ELISA in serum samples taken at the time of the first biopsies, and TGF-beta was determined semiquantitatively by immunostaining of liver biopsy sections. Fibrosis was scored blinded in the biopsy samples by two pathologists independently. There was a close correlation between TGF-beta serum levels and the rate of fibrosis progression. Patients with no progression of fibrosis had significantly lower (59 ng/mL +/- 22) TGF-beta serum levels than patients with progressive disease (115 ng/mL +/- 20), and a TGF-beta level below 75 ng/mL was predictive for stable disease. Immunohistology for TGF-beta in biopsy samples was also predictive for progressive liver disease with fibrosis progression found in those patients displaying staining of hepatocytes and sinusoidal cells. No such correlation was found with other markers such as procollagen III peptide, viral load or transaminase levels. These results further support the role of TGF-beta in liver fibrogenesis, and offer an opportunity to predict clinical disease progression, which may help in selecting patients who are in need of therapeutic interventions.

Alanine Transaminase↗
PubMed2001

Hippocampal lesions in the neuronal ceroid lipofuscinoses.

Epilepsy is a common manifestation in all childhood-onset forms of neuronal ceroid lipofuscinosis. In order to document hippocampal lesions and their relationship to epilepsy we studied autopsy specimens from the hippocampi of a series of patients with the infantile (CLN1), classic late infantile (CLN2), Finnish variant late infantile (CLN5), and juvenile (CLN3) neuronal ceroid-lipofuscinosis as well as Northern epilepsy (CLN8), using a battery of histological and immunocytochemical staining methods. Despite striking differences in the overall degree of neocortical neuronal storage and loss, these genetically heterogeneous forms of neuronal ceroid lipofuscinosis showed a common lesional pattern in the hippocampi: a relative sparing of the CA1 sector and severe involvement of the neighbouring CA2 sector, with intermediate degrees of involvement of the CA3 and CA4 sectors. These findings distinguish the hippocampal pathology associated with the neuronal ceroid lipofuscinoses from classical 'mesial temporal sclerosis' and show that the selective lesional pattern in the neuronal ceroid lipofuscinoses is not a secondary anoxic-ischaemic phenomenon. It is rather a consequence of the primary metabolic defects and may be directly involved in the causation of the epileptic discharges.

Child↗