Einleitung: Die Implantation kryokonservierter allogener Aortenklappen stellt heutzutage eine effektive operative Technik dar, um in schweren Fällen einer floriden Aortenklappenendokarditis exzellente postoperative Ergebnisse zu erzielen. Diese Studie demonstriert die Langzeitergebnisse im Deutschen Herzzentrum Berlin über einen Zeitraum von 17 Jahren. Material und Methoden: Zwischen dem 1.Januar 1987 und 31.Dezember 2003 wurden bei 203 Patienten mit florider Aortenklappenendokarditis kryokonservierte Aortenklappenallografts implantiert (in subkoronarer Implantationstechnik n=107 und durch totalen Aortenwurzelersatz n=96). Das mittlere Alter der Patienten betrug 51,3 Jahre (2-82 Jahre). Darunter waren 42 Frauen und 161 Männer. 161 Patienten zeigten präoperativ eine anuläre Aortenwurzelabszeßbildung. Ergebnisse: Die 30-Tage-Mortalität (mit Anulusabszeß) betrug insgesamt 21,1% (23,6%): bei nativer Aortenklappenendokarditis 14,9% (17,5%) und bei Prothesen-endokarditis 29,2% (29,6%). Nach 17 Jahren waren 70,4+3,6% und 78,6+6,3% (p=0,24) der Patienten mit und ohne präoperativem Anulusabszeß am Leben. Bei 12 Patienten mit Anulusabszeß trat eine Allograft-Re-Infektion auf, die aktualisierte Freiheit von Reinfektion betrug 91,6+2,4% nach 17 Jahren. Insgesamt wurden 37 Patienten reoperiert, die aktualisierte Freiheit von Reoperation betrug 75,0+3,7% nach 17 Jahren. Die aktualisierte Freiheit von Explantation der Allografts wegen Strukturalteration betrug bei den Patienten mit Anulusabszeß nach 17 Jahren 96,0+2,0%. Thrombembolische Ereignisse traten nicht auf. Die Univarianzanalyse identifizierte die Allograft-Re-Infektion (p=0,0001) und zu klein bemessene Allografts (p=0,001) als Risikofaktoren für eine Reoperation sowohl bei nativer als auch Prothesenendokarditis. Schlußfolgerung: Aortenklappenallografts zeigen bei florider Aortenklappenendokarditis mit Anulusabszeß exzellente Langzeitresultate. Die 30-Tage–Mortalität wird hinsichtlich der Schwere der Erkrankung akzeptiert und Re-Infektionen sind selten. Zu klein bemessene Allografts und Re-Infektionen sind Risikofaktoren für Reoperationen. / Objective: Cryopreserved aortic valve homografts have become an accepted valve substitute in acute aortic valve endocarditis, but long-term studies of valve function are largely unavailable. This survey represents our observations over a period of 17 years. Material and methods: Between February 9, 1987 and October 30, 2003, 203 patients with infective aortic valve endocarditis underwent allograft replacement of the aortic valve (free-hand subcoronary technique, n=107 and root replacement, n=96). The patients’ age ranged between 2 and 82 years with a mean age of 51.3 years. The survey included 42 females and 161 males. 161 had infected aortic root with ring abscesses. Results: The hospital mortality of patients with native and prosthetic endocarditis complicated by periannular abscess was 14.9% (17.5%) and 29.2 % (29.6%) respectively making an overall hospital mortality of 21.2% (23.6%). 17 years patient survival in patients with and without periannular abscess was 70.4+3.6% and 78.6+6.3% (p=0,24) respectively. There were 12 events of recurrent endocarditis in patients with periannular abscess, giving an actuarial freedom of 91.6+2.4% at 17 years. Reoperation was performed in 37 patients for a variety of reasons, and overall freedom from reoperation was 75.0+3.7% at 17 years. Freedom from explantation for structural valve deterioration was 96.0+2.0% at 17 years for patients with periannular abcess. No thrombembolic event was evident. Univariable analysis identified recurrent endocarditis (p=0.0001) and undersized allograft (p=0.001) as risk factors for reoperation for both native and prosthetic aortic valve endocarditis. No risk factors for hospital mortality were found. Conclusion: Aortic allograft offers an excellent long-term clinical result in patients with infective aortic valve endocarditis with associated periannular abscess. Operative mortality is acceptable based on the severity of aortic pathology, with low evidence of recurrent endocarditis and no thrombembolic events. Undersized allograft and recurrent infection are risk factors for reoperation.

Anfang der 90er Jahre entwickelten sich neue pharmakologische Behandlungsstrategien des akuten Myokardinfarktes durch GP IIb/IIIa- Rezeptorantagonisten. Der optimale Zeitpunkt der Administration und die Wahl des Therapieregimes ist Diskussionsstoff. Ziel dieses Konzeptes ist es, mit der Verlagerung des Therapiebeginns in die Prähospitalphase die Zeit bis zur Reperfusion des Infarktareals zu minimieren. Die Schaffung einer Hotline zum Kardiologen bietet dem Notarzt fachlichen Rat. Bestehen keine logistischen Hindernisse innerhalb von 60 Minuten wird eine Herzkatheteruntersuchung, bei Überschreiten wird die Kombinationslysetherapie mit interventioneller Versorgung des Infarktgefäßes binnen 24 Stunden durchgeführt. Ziel der Datenanalyse war nachzuweisen, ob die Sterblichkeit von bis zu 15% im Vergleich zu Registerstudien gleicher Konzeption niedriger und die Krankenhausverweildauer von 12 Tagen kürzer ist. Im Erfassungszeitraum wurden 347 Patienten, davon 254 Männer (73%) und 93 Frauen (27%) behandelt. Das Alter im Median betrug 62 Jahre. 57 (16%) Patienten wurden prähospital lysiert, 81 (20%) inhospital. 218 (63%) wurden mittels primärer interventioneller Therapie behandelt. Die Aufenthaltsdauer im Krankenhaus aller Patienten betrug 6 Tage. Der Aufenthalt im Median auf der Intensivstation betrug in der Gruppe der lysierten Patienten 1,0 Tage (prähospital 0,8 vs inhospital 1,3 Tage), in der primären Herzkathetergruppe 0,9 Tage. 8 MACE traten auf. Die Kankenhausmortalität betrug 6,3 %, in der Gruppe der mittels Lyse behandelten Patienten 9,3% (prähospital 12,3%, inhospital 6,9%) und in der primär interventionell versorgten Gruppe 4,6%. Die Mortalität der initial hämodynamisch stabilen Patienten lag unter 3%. Die 180 Tage Mortalität betrug gesamt 10,8%, in der Lyse Gruppe 11,7% (prähospital 14,0% vs. inhospital 9,9%) und 9,2% in der interventionell behandelten Gruppe. Zu keinem Zeitpunkt bestanden signifikante Unterschiede. Die aggressive Therapie des akuten Myokardinfarkts beinhaltet diesen Daten zufolge kein Risiko für die Patienten und zeigt im Vergleich zu Registerstudien ähnlicher Konzeption eine niedrigere Krankenhaussterblichkeit und eine kürzere Krankenhausverweildauer. Diese Arbeit ist der Erinnerung an meinem geschätzten Freund und Kollegen Oberarzt Dr. med. Torsten Thieme gewidmet, der viel zu früh verstorben ist. / In the early 90’s a new class of agents blocking the GPIIb/IIIa-receptors on the platelet surface was developed capable of speeding up pharmacological reopening of infarct related arteries. The optimal time of administration remains subject of discussion. Despite these advantages hospital mortality in great registries is still more than 15% and hospital stay 12 days. By January 1st, 1999 a hotline between ambulance car and the interventional cardiologist was instituted. In each case management with either immediate PCI under GPIIb/IIIa-inhibition or half dose thrombolytics and full dose GPIIb/IIIa-inhibitors, if possible, started out of hospital. The approach was to see if the mortality was lower and the hospital stay shorter than in comparable registries. During September 1999 – December 2001 347 patients aged 26 to 92 years (60 plus minus 13) were treated. Median age was 62 years. There were 93 female (27%) and 254 male patients (73%). 57 (16%) patients received out of hospital thrombolysis, 81 (20%) were treated inhospital and 218 (63%) patients underwent primary cardiac catheterization. Overall inhospital median stay was 6.0 days. The median ICU-time for all thrombolysed patient was 1,0 days (prehospital 0,8 vs inhospital 1,3 days) and in the interventionally treated group 0,9 days. In all patients .8 MACE events occurred. Overall hospital mortality was 6,3 %, in the group of thrombolysed patients 9,3% (prehospital 12,3%, inhospital 6,9%). Shock excluded mortality was below 3%. 346/347 patients reached 180 days of follow-up. 180 days mortality overall was 10,8%, for the thrombolysed group 11,7% (prehospital 14,0% vs. inhospital 9,9%) and 9,2% in the interventionally treated group. There was no statistical significant difference. The time optimized individualized treatment assignment to pharmacological therapy followed by routine facilitated PCI within 24 hours is an approach that is more aggressive than currently recommended in the guidelines, but seems to offer further improvements of outcome with no further riscs for patients with AMI in comparison to other registries. This work is published in memory of my beloved friend and colleague Torsten Thieme, MD, who died much to young.

Die Therapie des häufigsten primären Hirntumors bei Erwachsenen, des Glioblastoms, gestaltet sich aufgrund der relativen Resistenz gegen Bestrahlung und Zytostatika schwierig und resultiert in einer äußerst schlechten Prognose. Ziel dieser Arbeit war die Identifikation von zellulären Faktoren, die bei einer Behandlung mit dem neuartigen onkolytischen Virus Ad5-Delo3RGD (ΔE1A-13S, ΔE19K, ΔE3, zusätzliches RGD-Motiv) eine Bedeutung hinsichtlich des Ansprechens auf die Therapie haben. Dazu erfolgte nach der Transduktion von Gliomzellen mit adenoviralen Vektoren, mit unterschiedlichem E1A-Status, eine Analyse der Modulation der globalen Genexpression. Die E1A-Deletante, Ad5-Ad312, war replikationsinkompetent in Gliomzellen und hatte infolgedessen nur einen marginalen Einfluss auf Genebene und keine biologischen Effekte auf Proteinebene. Das Wildtypvirus (Ad5-wt) mit intakter und das onkolytische Virus (Ad5-Delo3RGD) mit mutierter E1A-Region induzierten eine starke Modifikation der zellulären Genexpression in Gliomzellen. Die Transduktion der Gliomzellen mit Wildtypvirus bzw. onkolytischen Virus resultierte in einer bis zu 60 %-igen Hemmung der Sekretion des Angiogenesefaktors VEGF. Fernerhin konnte in Glioblastomzellen gezeigt werden, dass Ad5-wt und Ad5-Delo3RGD eine 50 bis 60 %-ige Inhibition der Sekretion von TGF-β2, sowie eine bis zu 65 %-ige Hemmung der Transkriptionsaktivität des TGF-β-Signalwegs induzierten. Damit reprimieren besagte Viren zelluläre Faktoren, deren Expression im Gliom mit einer schlechten Prognose korreliert ist. Aufgrund dieser Daten konnte für maligne Gliome ein Modell von Ad5-Delo3RGD-Therapie relevanten zellulären Faktoren entwickelt werden, welches den Zusammenhang zwischen TGF-β2, VEGF bzw. MIR-181 und der Virotherapie verdeutlicht. Mit Hilfe dieses Modells steigt das Verständnis um die antineoplastische Aktivität des onkolytischen Virus, und ermöglicht damit eine Verbesserung der Ad5-Delo3RGD-basierten Therapie. / Glioblastoma is the most common type of brain tumor among adults. The therapy is very difficult, due to its relative resistance to radiation and zytostatica, and often results in fatal prognosis. The main objective of this thesis was the identification of cellular factors associated with therapy response to adenoviral treatment using the newly developed oncolytic virus Ad5-Delo3RGD. Therefore, after viral transduction of glioma cells with adenoviral vectors, using E1A-wildtype and -mutant viruses, an analysis of the modulation of mRNA expression profiles was conducted. The E1A deletion mutant Ad5-Ad312 was replication-deficient in glioma cells and therefore had only marginal influence of host gene transcription level and no biological effect on protein level. Both, wildtype adenovirus type 5 (Ad5-wt), with intact E1A, and oncolytic virus (Ad5-Delo3RGD), with mutated E1A, induced strong modifications of gene expression profiles in glioma cells. The transduction of glioma cells with wildtype or oncolytic virus resulted in a 60 % reduced secretion of the angionesis factor Vascular Endothelial Growth Factor (VEGF). In addition it was shown that Ad5-wt and Ad5-Delo3RGD induced a reduced secretion of TGF-ß2 by 50 to 60 % and a repression of the SMAD2/SMAD3/SMAD4-specific transcription activity up to 65 %. Thus the viruses inhibit cellular factors, which expression is corelated to a weak prognosis. Based on this data a new model for malign glioma was developed, which illustrates the relationship between virotherapy and the cellular factors TGF-β2, VEGF and MIR-181, which are associated with treatment response to Ad5-Delo3RGD-based therapy. The model helps to understand the basic antineoplastic activity of the oncolytic virus and therefore should help to improve Ad5-Delo3RGD-based therapy.

Beim Tissue Engineering werden Erkenntnisse aus der Medizin, Biologie und Chemie mit Methoden der Ingenieurwissenschaften kombiniert, um biologische Ersatzgewebe herzustellen. Das Konzept besteht darin, aus körpereigenen Zellen einen vitalen und funktionalen Gewebeersatz zu fertigen. Hierbei werden körpereigene Zellen auf ein resorbierbares Gerüst transplantiert, in vitro zu einer stabilen Struktur gefestigt, um letztendlich ein vitales Ersatzgewebe implantieren zu können. Die Konstrukte für die menschliche Herzchirurgie sollten in das umgebende Gewebe einwachsen und haben das Potential sich wie gesundes Gewebe zu entwickeln und mitzuwachsen. / Tissue engineering combines knowledge from the fields of medicine, biology and chemistry with the methods of engineering to create artificial tissue. The concept is to produce vital and functional tissue from endogenous cells. These are seeded on to an absorbable scaffold and consolidated to form a stable structure in vitro, with the aim of eventually being able to produce substitute tissue for implantation. The constructs for human cardiac surgery need to embed into the surrounding tissue and, just like natural tissue, to have the potential to grow and develop.

Tumoren entwickeln während einer Chemotherapie häufig Resistenzen gegen strukturell und funktionell unabhängige Zytostatika - ein Phänomen, das als Multidrug-Resistenz (MDR) bezeichnet wird und die Hauptursache für das Scheitern einer Chemotherapie ist. Die klassische MDR ist mit einer Überexpression des ABC-Transporters MDR1/P-gp assoziiert. Der vorliegende gentherapeutische Ansatz beinhaltet eine selektiv gegen MDR1/P-gp gerichtete und vor allem effiziente Strategie zur Überwindung des MDR-Phänotyps humaner Tumorzellen. Basierend auf der Integration verschiedener anti-MDR1 shRNA Expressionskassetten in adenovirale Gentherapievektoren, konnte mit Hilfe der RNA-Interferenz Technologie (RNAi) die MDR1/P-gp Expression selektiv inhibiert werden. Mittels des hoch effizienten Adenovirus Ad5U6/MDR-C wurde die MDR1 mRNA- sowie Protein-Expression soweit reprimiert, dass eine vollständige Aufhebung der biologischen Aktivität der Effluxpumpe MDR1/P-gp und eine Reversion des Resistenz Phänotyps gegenüber den typischen MDR1/P-g-Substraten Daunorubicin (87 % in EPP85-181RDB bzw. 66 % in EPG85-257RDB) sowie Vincristin (96 % bzw. 82 %) resultierte. Zudem wurde gezeigt, dass E1-deletierte und damit replikationsinkompetente Adenoviren in multidrug-resistenten Tumorzellen replizieren können. Damit wirkt Ad5U6/MDR-C in MDR-Tumorzellen onkolytisch. Zwar konnte die Adenovirusreplikation mit dem DNA-Synthese-Hemmer Hydroxyurea (HU) zu 94 % inhibiert werden, die anti-MDR1 Effizienz von Ad5U6/MDR-C wurde dennoch erhöht (+5 % in HeLaRDB, +12 % in EPG85-257RDB), was für eine erfolgreiche und niedrig dosierte Ad-Gentherapie multidrug-resistenter Tumoren in Kombination mit HU ausgenutzt werden kann. Außerdem wurde der entscheidende Einfluss des regulatorischen Proteins YB-1 auf die selektive Replikation von Ad5U6/MDR-C in MDR1/P-gp überexprimierenden Tumorzellen gezeigt. Eine 90 %ige Inhibition von YB-1 bedingt eine Hemmung der Adenovirusreplikation um 70 % und damit eine verringerte Effizienz der RNAi-vermittelten Inhibition von MDR1/P-gp um 40 %. Mit diesem gentherapeutischen Ansatz können die Effekte der YB-1-abhängigen und der die Zelllyse bedingenden Adenovirusreplikation sowie der anti-MDR1 shRNA vermittelten Chemosensitivierung kombiniert und zu einer verbesserten Eliminierung von MDR-Tumorzellen führen. / Simultaneous resistance of cancer cells to multiple cytotoxic drugs, multidrug resistance (MDR), is the major limitation to the successful chemotherapeutic treatment of disseminated neoplasms. The ‘classical’ MDR phenotype is conferred by MDR1/P-glycoprotein (MDR1/P-gp) that is expressed in almost 50% of human cancers. Recent developments in the use of small interfering RNAs for specific inhibition of gene expression have highlighted their potential use as therapeutic agents. DNA cassettes encoding RNA polymerase III promoter-driven siRNA-like short hairpin RNAs (shRNAs) allow long-term expression of therapeutic RNAs in targeted cells. A variety of viral vectors have been used to deliver such cassettes to mammalian cells. In this study, the construction of different adenoviruses for anti- MDR1/P-gp shRNA delivery in different human multidrug-resistant cancer cells was investigated. It could be demonstrated that MDR1/P-gp mRNA and protein expression could be completely inhibited by adenoviral delivery of anti-MDR1/P-gp shRNAs. This down regulation in mRNA and protein expression was accompanied by a complete inhibition of the pump activity of MDR1/P-gp and a reversal of the multidrug-resistant phenotype. Moreover, it could be demonstrated that MDR-tumour cells facilitate adenoviral replication of originally E1- and E3-deleted and thus replication deficient adenoviral vectors through stable relocation of the fundamental regulatory factor YB-1 to the nucleus. To analyse the impact of YB-1 on adenoviral replication, two specific in vitro MDR models were used which stably trigger YB-1 posttranscriptional gene-silencing via the RNA interference (RNAi) pathway, i.e. the MDR cell line EPG85-257RDB well as its drug-sensitive counterpart EPG85-257P. The YB-1 gene-silencing effects of 90 % were accompanied by a reduction of adenoviral gene expression of 70 %. In conclusion, the data demonstrate that an highly efficient adenoviral delivery of shRNAs can chemosensitise human cancer cells and that YB-1 is involved in the regulation of adenoviral gene expression of originally replication deficient Ad-vectors in MDR cancer cells.

Fiber amplifiers with high power and high pulse energy are strongly in demand for both scientific research and industrial applications. Ytterbium-doped fiber has been an outstanding choice for its broad-gain bandwidth and excellent power conversion efficiencies. In this dissertation, we introduced a compact high power high pulsed energy laser system with chirally coupled core (3C) Yb-doped fibers as the gain media. Traditional standard fibers and photonic crystal fibers are not suitable for compact high power high pulse energy laser systems because of poor higher order modes (HOMs) management and complicated air-hole structure. Newly invented 3C silica fibers solve these problems. A helical side-core around the Yb-doped central core extracts the HOMs from the central core. By adjusting this chirally structure, the core of the 3C fiber can be enlarged and the transverse mode of the fiber can be single mode at certain wavelengths. To simulate the amplification process with high power high pulse energy better, a new modeling method based on a combination of the rate equations and the nonlinear Schrödinger equations is invented. The gain was calculated from rate equations and the pulse evolution was analyzed using nonlinear Schrödinger equation. The simulation provided a good guidance for building compact high power high pulse energy laser systems. To achieve high power and high pulse energy, the system is designed as a two-stage structure. The laser

<p>As a means of further localising the interaction, truncated fragments derived from the C-terminal region of YB-1, were tested for their interaction with the RING finger domain of RBBP6 using three different assays: a directed yeast 2-hybrid assay, co-immunoprecipitation and NMR chemical shift perturbation analysis. Our results suggest that the entire 62 amino acid region at the C-terminal domain of YB-1 may be involved in the interaction with RBBP6. Using chemical shift perturbation analysis, this study provides an indication of where YB-1 binds to the RING finger. This represents the first step towards the design of therapeutics aimed at modulating the interaction between RBBP6 and YB-1 as a means of targeting the oncogenic effects of YB-1. In order to identify E2 enzymes involved in the ubiquitination of YB-1, we examined the efficiencies of selected E2s in an in vitro ubiquitination assay. UbcH5c and UbcH7 were both found to catalyse the ubiquitination of YB-1 in conjuction with RBBP6, whereas Ubc13 was not. Finally, we show using NMR that two single-point mutations of the RING finger-like domain are sufficient to abolish homodimerisation of the domain. These will be used in future studies to investigate the requirement for homodimerisation on the ubiquitination activity of RBBP6.</p>

<p>As a means of further localising the interaction, truncated fragments derived from the C-terminal region of YB-1, were tested for their interaction with the RING finger domain of RBBP6 using three different assays: a directed yeast 2-hybrid assay, co-immunoprecipitation and NMR chemical shift perturbation analysis. Our results suggest that the entire 62 amino acid region at the C-terminal domain of YB-1 may be involved in the interaction with RBBP6. Using chemical shift perturbation analysis, this study provides an indication of where YB-1 binds to the RING finger. This represents the first step towards the design of therapeutics aimed at modulating the interaction between RBBP6 and YB-1 as a means of targeting the oncogenic effects of YB-1. In order to identify E2 enzymes involved in the ubiquitination of YB-1, we examined the efficiencies of selected E2s in an in vitro ubiquitination assay. UbcH5c and UbcH7 were both found to catalyse the ubiquitination of YB-1 in conjuction with RBBP6, whereas Ubc13 was not. Finally, we show using NMR that two single-point mutations of the RING finger-like domain are sufficient to abolish homodimerisation of the domain. These will be used in future studies to investigate the requirement for homodimerisation on the ubiquitination activity of RBBP6.</p>

Philosophiae Doctor - PhD / Retinoblastoma Binding Protein 6 (RBBP6) is a 250 kDa multi-domain protein that has been implicated in diverse cellular processes including apoptosis, mRNA processing and cell cycle regulation. Many of these functions are likely to be related to its interaction with tumour suppressor proteins p53 and the Retinoblastoma protein (pRb), and the oncogenic Y-Box Binding Protein-1 (YB-1). RBBP6 inhibits the binding of p53 to DNA and enhances the HDM2-mediated ubiquitination and proteasomal degradation of p53. Disruption of RBBP6 leads to an embryonic lethal phenotype in mice as a result of widespread p53-mediated apoptosis. RBBP6 promotes ubiquitination and degradation of YB-1, leading to its proteasomal degradation in vivo.The first part of this thesis describes in vitro investigations of the interaction betweenbacterially-expressed human p53 and fragments of human RBBP6 previously identified as interacting with p53, in an attempt to further localise the region of interaction on both proteins. GST-pull down assays and immunoprecipitation assays confirmed the interaction, and localised it to the core DNA binding domain of p53 and a region corresponding to residues 1422-1668 of RBBP6. However in Nuclear Magnetic Resonance (NMR) chemical shift perturbation assays no evidence was found for the interaction. NMR showed the relevant region of RBBP6 to be unfolded,and no evidence was found for interaction-induced folding. The R273H mutant of the p53 core domain did not abolish the interaction, in contrast to reports that the corresponding murine mutation (R270C) did abolish the interaction.The second part of this thesis describes in vitro investigations of the ubiquitination of YB-1 by RBBP6. A fragment corresponding to the first 335 residues of RBBP6,denoted R3, was expressed in bacteria and found to be soluble. Contrary to expectation, in a fully in vitro assay R3 was not able to ubiquitinate YB-1. However,following addition of human cell lysate, YB-1 was degraded in an R3-dependent and proteasome-dependent manner, indicating that R3 is required for ubiquitination and proteasomal degradation of YB-1. However R3 is not sufficient, with one or more factors being supplied by the cell lysate. In view of the pro-tumourigenic effects of YB-1 in many human cancers, these results lay the foundation for an understanding of the regulatory effect of RBBP6 on YB-1 and its potential role in anti-tumour therapy.

>Magister Scientiae - MSc / In the past few decades, the studies of f-electron materials have revealed unusual physical properties such as Fermi-liquid, non-Fermi-liquid behaviour at low temperatures, heavy- Fermion behaviour, valence fluctuation, Kondo effect, superconducting and magnetic ordering. These materials include binary and ternary compounds and alloys with Cerium (Ce) or Ytterbium (Yb) based rare earth elements or Uranium (U) based actinide element. In these systems the localized magnetic moments formed by Ce, Yb or U ions transform the electronic properties of these compounds leading to quasiparticles with masses in excess to 1000 times the bare electron mass. These materials are known as heavy-fermion materials. Two well known heavy – Fermion compounds with Ce based rare earth elements of interest in this thesis are CePt₂Si₂ and CeCu₅In. The effect of substituting Ce with moment bearing Tb or Dy in these two compounds, are reported through measurements of electrical resistivity, magnetic susceptibility and magnetization. The three alloy systems (Ce₁₋ₓREₓ)Pt₂Si₂ (RE = Tb, Dy) and (Ce₁₋ₓTbᵪ)Cu₅In under investigation in the present thesis, was synthesized and characterized by x-ray diffraction. The alloy systems (Ce₁₋ₓREₓ)Pt₂Si₂ (RE = Tb, Dy, 0≤ ᵡ ≤1) formed a single phase in the P4/nmm tetragonal CaBe₂Ge₂ – type structure across the whole series while the (Ce₁₋ₓTbᵪ)Cu₅In alloy system formed a single phase in the Pnma orthorhombic CeCu₆ – type crystal structure up to 40% Ce substitution. The physical properties of these systems is reported and discussed through the measurements of electrical resistivity, magnetic susceptibility and magnetization. The variables of this study are: the doping concentration of Tb or Dy, the applied magnetic field and the sample temperature. Electrical resistivity studies for all the systems revealed coherence effect at Ce – rich alloys (0≤ ᵡ ≤0.2) and single-ion Kondo scattering with further increased RE concentration ( ᵡ ≥ 0.3). The magnetic property studies indicate antiferromagnetic ordering only for the (Ce₁₋ₓREₓ)Pt₂Si₂ alloy system in the concentration range 0.7≤ ᵡ ≤ 1. The present thesis is comprised of six chapters, which are arranged as follows: The first chapter deals with the theoretical background of the physical properties of Ce based intermetallics compounds and alloys. Experimental techniques constitutes chapter II and explains the techniques used in this study. The theoretical overview of the two parent compounds of interest in this thesis (CePt₂Si₂ and CeCu₅In) is presented in chapter III. The fourth and the fifth chapters of this study deals with results and discussion. The thesis is completed with a conclusion in chapter six.