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Biomedical subjects

J Müller

Publications and source records attributed to J Müller.

At least 91 records · Page 5Linked to original sources
PubMed2002

Prepubertal growth in congenital disorder of glycosylation type Ia (CDG-Ia).

AIMS: To delineate the pattern of growth in prepubertal children with congenital disorder of glycosylation type Ia (CDG-Ia) in order to identify critical period(s) and possible cause(s) of growth failure. METHODS: Longitudinal measurements of weight, length/height, and head circumference from birth to 10 years of age in 25 CDG-Ia patients with the R141H/F119L PMM2 genotype were analysed. The data and derived body mass indices (BMI) were compared with standards and expressed as standard deviation scores (SDS). A linear mixed effects model was fitted to each set of data, and mean curves were estimated. RESULTS: The mean weight SDS decreased from -0.3 at birth to -3.0 at 7 months of age and remained low or increased slightly. The mean length SDS decreased from zero at birth to -2.4 at 7 months of age followed by a slight increase to a maximum of -1.8 SDS at the end of the second year of life. After age 2 the mean length/height SDS decreased again. The mean BMI SDS at birth was -0.7 and declined to a minimum of -2.8 at the end of the second year of life followed by a gradual increase. The mean head circumference SDS declined gradually from 0 at 3 months of age to -1.9 at age 5. CONCLUSION: CDG-Ia patients with the R141H/F119L genotype have normal fetal growth and an immediate postnatal onset of severe growth failure. A notable decline in weight end length SDS takes place during the first seven months of life with no prepubertal catch up.

Adolescent↗
PubMed2002

Iatrogenic adrenal insufficiency as a side-effect of combined treatment of itraconazole and budesonide.

A recent case of iatrogenic Cushing's syndrome and complete suppression of the pituitary-adrenal-axis in a patient with cystic fibrosis (CF) and allergic bronchopulmonary aspergillosis treated with itraconazole as an antifungal agent, and budesonide as an anti-inflammatory agent led to a systematic assessment of this axis and gonadal function in all patients treated with itraconazole in the authors' CF centre. Itraconazole can inhibit CYP3A, thus interfering with synthesis of gluco- and mineralocorticoids, androgens and oestradiol as well as the metabolism of budesonide. The aim of this study was to evaluate adrenal and gonadal function in patients treated with itraconazole with or without budesonide. An adrenocorticotrophic hormone (ACTH) test (250 microg tetracosactid) was performed in 25 CF patients treated with both itraconazole and budesonide, and in 12 patients treated with itraconazole alone (six patients with CF and six with chronic granulomateous disease). Mineralocorticoid and gonadal steroid function were evaluated by measurements of plasma-renin, follicle stimulating hormone, luteinising hormone, progesterone, oestradiol, testosterone, serum-inhibin A and B. ACTH tests performed as part of a pretransplantation programme in an additional 30 CF patients were used as controls. Eleven of the 25 patients treated with both itraconazole and budesonide had adrenal insufficiency. None of the patients on itraconazole therapy alone nor the control CF patients had a pathological ACTH test. Mineralocorticoid and gonadal insufficiency was not observed in any of the patients. Only one patient with an initial pathological ACTH-test subsequently normalised, the other 10 patients improved but had not achieved normalised adrenal function 2-10 months after itraconazole treatment had been discontinued. Suppression of the adrenal glucocorticoid synthesis was observed in 11 of 25 cystic fibrosis patients treated with both itraconazole and budesonide. The pathogenesis is most likely an itraconazole caused increase in systemic budesonide concentration through a reduced/inhibited metabolism leading to inhibition of adrenocorticotrophic hormone secretion along with a direct inhibition of steroidogenesis. In patients treated with this combination, screening for adrenal insufficiency at regular intervals is suggested.

Adolescent↗
PubMed2001

Cytochrome c oxidase deficiency due to mutations in SCO2, encoding a mitochondrial copper-binding protein, is rescued by copper in human myoblasts.

Mutations in SCO2, a cytochrome c oxidase (COX) assembly gene, have been reported in nine infants with early onset fatal cardioencephalomyopathy and a severe COX deficiency in striated muscle. Studies on a yeast homolog have suggested that human Sco2 acts as a copper chaperone, transporting copper to the Cu(A) site on the Cox II subunit, but the mechanism of action remains unclear. To investigate the molecular basis of pathogenesis of Sco2 defects in humans we performed genetic and biochemical studies on tissues, myoblasts and fibroblasts from affected patients, as well as on a recombinant human C-terminal Sco2 segment (22 kDa), bearing the putative CxxxC metal-binding motif. Recombinant Sco2 was shown to bind copper with a 1:1 stoichiometry and to form homomeric complexes in vitro, independent of the metal-binding motif. Immunohistochemistry using antibodies directed against different COX subunits showed a marked tissue-specific decrease in the Cox II/III subunits that form part of the catalytic core, consistent with the differential tissue involvement, but a more uniform distribution of Cox Vab, a nuclear-encoded subunit. Sco2 was severely reduced in patient fibroblasts and myoblasts by immunoblot analysis. Patient fibroblasts showed increased (64)Cu uptake but normal retention values and, consistent with this, the copper concentration was four times higher in Sco2-deficient myoblasts than in controls. COX activity in patient myoblasts was completely rescued by transduction with a retroviral vector expressing the human SCO2 coding sequence, and more interestingly by addition of copper-histidine (300 microM) to the culture medium. Whether the latter is accomplished by the very low residual levels of Sco2 in the patient cells, direct addition of copper to the Cu(A) site, or by another copper-binding protein remains unknown. Whatever the mechanism, this result suggests a possible therapy for the early treatment of this fatal infantile disease.

Amino Acid Motifs↗
PubMed2001

Influence of gender on auditory startle responses.

The auditory startle reaction is considered a brainstem reflex in response to an unexpected loud stimulus. It may be abnormal in various neurological conditions. However, the influence of gender on physiological characteristics of auditory startle responses (ASRs) in humans has to date been studied only in orbicularis oculi muscle. We investigated 54 healthy adult subjects (27 males, 27 females). ASRs were elicited by binaural high-intensity auditory stimuli which differed randomly in tonal frequency and intensity (250 Hz-90 db; 500 Hz-105 dB; 750 Hz-110 db, 1000 Hz-110 dB nHL), presented through tubal insert phones. Reflex electromyographic activity was simultaneously recorded with surface electrodes from masseter, orbicularis oculi, sternocleidomastoid, biceps brachii, abductor pollicis brevis, rectus femoris, tibialis anterior, and soleus muscles. ASR probability was significantly lower, and ASR area under the curve was significantly smaller, in men versus women. Median onset latencies did not differ significantly, but tended to be shorter in the lower extremities of men despite greater body height. Habituation, measured as a reduction in response probability with repeated stimulation, was significant in all muscles except orbicularis oculi in both men and women. Our data provide evidence for a significant influence of gender on ASR characteristics. The observed differences are likely due to gender-specific variations of central processing in the brainstem centers involved in ASR generation, and should be taken into account when testing ASRs in health and disease.

Acoustic Stimulation↗
PubMed2001

Structure of a fast kinesin: implications for ATPase mechanism and interactions with microtubules.

We determined the crystal structure of the motor domain of the fast fungal kinesin from Neurospora crassa (NcKin). The structure has several unique features. (i) Loop 11 in the switch 2 region is ordered and enables one to describe the complete nucleotide-binding pocket, including three inter-switch salt bridges between switch 1 and 2. (ii) Loop 9 in the switch 1 region bends outwards, making the nucleotide-binding pocket very wide. The displacement in switch 1 resembles that of the G-protein ras complexed with its guanosine nucleotide exchange factor. (iii) Loop 5 in the entrance to the nucleotide-binding pocket is remarkably long and interacts with the ribose of ATP. (iv) The linker and neck region is not well defined, indicating that it is mobile. (v) Image reconstructions of ice-embedded microtubules decorated with NcKin show that it interacts with several tubulin subunits, including a central beta-tubulin monomer and the two flanking alpha-tubulin monomers within the microtubule protofilament. Comparison of NcKin with other kinesins, myosin and G-proteins suggests that the rate-limiting step of ADP release is accelerated in the fungal kinesin and accounts for the unusually high velocity and ATPase activity.

Adenosine Triphosphatases↗
PubMed2001

[Non-invasive monitoring of rejection after cardiac transplantation. The method and retrospective analysis of data on 734 patients].

BACKGROUND AND OBJECTIVE: Endomyocardial biopsy is the gold standard for monitoring rejection in cardiac recipients. The death rate due to rejection with this invasive method is 5-6 % in the first postoperative year. The aim of this retrospective data analysis from cardiac recipients was to prove the diagnostic reliability of a non-invasive electrophysiological method for rejection monitoring. PATIENTS AND METHODS: We daily analyzed the QRS-complex amplitude of the intramyocardial electrogram, which we received over a period from one year via a pacemaker with a telemetric capability. The diagnostic guideline for a suspected rejection was the reduction of the QRS-complex amplitude by more than 8 %. Out of 734 patients 558 were included in the study. Biopsy was only performed when the non-invasive rejection monitoring data (QRS-complex amplitude plus echocardiography) showed a discrepancy for rejection. RESULTS: None of the patients died due to rejection, 273 at least once underwent a biopsy, and 285 never had a biopsy. The method reached a sensitivity of 0.9777, a specificity of 0.9634, a negative predictive value of 0.9850, and a positive predictive value of 0.9459. CONCLUSION: Daily electrophysiological non-invasive monitoring of rejection seems to be superior to endomyocardial biopsy. Death of patients due to rejection can be minimised. The number of necessary biopsies can be drastically reduced when compared to the usual number performed.

Adolescent↗
PubMed2001

Reliability of tissue Doppler wall motion monitoring after heart transplantation for replacement of invasive routine screenings by optimally timed cardiac biopsies and catheterizations.

BACKGROUND: Invasive screenings at predefined time intervals for acute rejection and transplant coronary artery disease (TxCAD) are standard procedures. However, cardiac biopsies and catheterizations are distressing and risky for the patients and are also costly. We assessed the reliability of pulsed-wave tissue Doppler imaging (PW-TDI) for the timing of invasive examinations in heart recipients in an attempt to avoid unnecessary endomyocardial biopsies (EMBs) and catheterizations. METHODS AND RESULTS: PW-TDI obtained at the basal left ventricular posterior wall before 408 EMBs and 293 catheterizations was tested for its diagnostic value regarding rejection and TxCAD with the use of International Society of Heart and Lung Transplantation biopsy grading, coronary angiography, and intravascular ultrasound as standards. Early diastolic peak wall motion velocity and relaxation time showed high sensitivities for clinically relevant rejection diagnosis (90.0% and 93.3%, respectively). The negative and positive predictive values for rejection of diastolic parameter changes appeared high enough (up to 96% and 92%, respectively) to allow a reliable noninvasive PW-TDI monitoring with efficiently timed, instead of routinely scheduled, EMBs. At definite cutoff values for systolic parameters, the probability for TxCAD reached 92% to 97%. The Fisher classification functions allowed TxCAD exclusion with 80% probability. CONCLUSIONS: Without diastolic parameter changes, acute rejection can be practically excluded, and serial PW-TDI can save patients from routine EMBs. The high specificity and negative predictive value for TxCAD of reduced systolic peak velocities and extended systolic time allow optimized timed catheterizations. Peak systolic velocity and systolic time allow diagnostic classifications that enable patients without known TxCAD but with high risk for catheterization to be spared routine angiographies.

Adult↗
PubMed2001

Influence of age on auditory startle responses in humans.

The auditory startle reaction is considered a brainstem reflex in response to an unexpected loud stimulus. We investigated the influence of age on auditory startle responses (ASRs) in 54 adult healthy subjects separated in three age groups (below 30; 30 to 50; above 50 years). ASRs were elicited by auditory stimuli randomly presented through tubal insert phones. Reflex electromyographic activity was simultaneously recorded from eight facial, neck, and extremity muscles. ASR probability was lower in extremity muscles of younger versus older subjects, but did not differ among age groups in facial and neck muscles. Median ASR latencies were significantly shorter in all muscles of younger versus older subjects. Our data provide evidence of a significant influence of age on ASRs. The observed differences are likely due to age-specific variations of central processing in the brainstem centers involved in ASR generation.

Acoustic Stimulation↗
PubMed2001

Discrete cleavage motifs of constitutive and immunoproteasomes revealed by quantitative analysis of cleavage products.

Proteasomes are the main proteases responsible for cytosolic protein degradation and the production of major histocompatibility complex class I ligands. Incorporation of the interferon gamma--inducible subunits low molecular weight protein (LMP)-2, LMP-7, and multicatalytic endopeptidase complex--like (MECL)-1 leads to the formation of immunoproteasomes which have been associated with more efficient class I antigen processing. Although differences in cleavage specificities of constitutive and immunoproteasomes have been observed frequently, cleavage motifs have not been described previously. We now report that cells expressing immunoproteasomes display a different peptide repertoire changing the overall cytotoxic T cell--specificity as indicated by the observation that LMP-7(-/-) mice react against cells of LMP-7 wild-type mice. Moreover, using the 436 amino acid protein enolase-1 as an unmodified model substrate in combination with a quantitative approach, we analyzed a large collection of peptides generated by either set of proteasomes. Inspection of the amino acids flanking proteasomal cleavage sites allowed the description of two different cleavage motifs. These motifs finally explain recent findings describing differential processing of epitopes by constitutive and immunoproteasomes and are important to the understanding of peripheral T cell tolerization/activation as well as for effective vaccine development.

Amino Acid Sequence↗
PubMed2001

Platinum and rhodium concentrations in airborne particulate matter in Germany from 1988 to 1998.

Increases in platinum group element (PGE) concentrations in ambient air and dust since the introduction of automotive catalytic converters in 1988 is a cause of concern. Until now, data derived from engine-test bench experiments have provided the basis for the assessment of human health risks associated with PGE exposure. Such experiments have provided valuable information regarding emission data that has been used to estimate ambient exposure concentrations. However, these data are not necessarily representative of typical environmental PGE exposure levels and conditions. Data on measured environmental concentrations is needed to provide a more adequate basis for the assessment of exposure and related risks. Twenty air and airborne-dust samples were provided by the Umweltbundesamt (Federal Environmental Agency, Germany) in the years 1988, 1989, 1992, 1997, and 1998. The samples were collected in Frankfurt/Main and the adjacent city of Offenbach. For this, 11 to 80 m3 of air were filtered over a 24-72 h period using a vacuum. Glass-fiber filters were used to collect samples. Sample platinum and rhodium concentrations were determined using adsorptive voltammetry. Although the number of samples collected in different years is limited, the results indicate a trend toward continuous increases in ambient concentrations of these metals between 1988 and 1998. Specifically, there were 46- and 27-fold increases in Pt and Rh concentrations, respectively. Despite these observed increases, the Pt concentrations measured (i.e., 147 pg/m3 on average, with a maximum of 246 pg/m3 in 1998) fell far below 15,000 pg/m3, which has been suggested as a guidance value (i.e., exposure at this level would be expected to be without appreciable health risk). The results of a particle-size distribution analysis of one sample (8-step impactor) that was collected 150 m away from a street show that approximately 75% of Pt and 95% of Rh occurs in association with large particulate matter of > 2 microns, with concentrations reaching a maximum in particles of 4.7 to 5.8 microns. The remaining 25% of Pt and 5% of Rh is present in fine particulate matter of < 2 microns. An approximate 10% of Pt and < 38% of Rh in airborne particles was found to be soluble in 0.1 molar HCl. Further, the results indicate that most of the emitted PGE particles from automotive catalytic converters, particularly those bound to fine particulate matter, are capable of being airborne. As a result, PGEs are not only present in areas close to emissions (e.g., roads), but can be transported over longer distances.

Air Movements↗
PubMed2001

Formation of ternary complexes by coordination of (diethylenetriamine)-platinum(II) to N1 or N7 of the adenine moiety of the antiviral nucleotide analogue 9.

The synthesis of (Dien)Pt(PMEA-N1), where Dien = diethylenetriamine and PMEA2- = dianion of 9-[2-(phosphonomethoxy)ethyl]adenine, is described. The acidity constants of the threefold protonated H3[(Dien)Pt(PMEA-N1)]3+ complex were determined and in part estimated (UV spectrophotometry and potentiometric pH titration): The release of the proton from the (N7)H+ site in H4[(Dien)Pt(PMEA-N1)]3+ occurs with a rather low pKa (= 0.52+/-0.10). The release of the proton from the -P(O)2(OH) group (pKa = 6.69+/-0.03) in H[(Dien)Pt(PMEA-N1)]+ is only slightly affected by the N1-coordinated (Dien)Pt2+ unit. Comparison with the acidic properties of the H[(Dien)Pt(PMEA-N7)]+ species provides evidence that in the (Dien)Pt(PMEA-N7) complex in aqueous solution an intramolecular, outer-sphere macrochelate is formed through hydrogen bonds between the -PO3(2-) residue of PMEA2- and a PtII-coordinated (Dien)NH2 group; its formation degree amounts to about 40%. The stability constants of the M[(Dien)Pt(PMEA-N1)]2+ complexes with M2+ = Mg2+, Ca2+, Ni2+, Cu2+ and Zn2+ were measured by potentiometric pH titrations in aqueous solution at 25 degrees C and I = 0.1 M (NaNO3). Application of previously determined straight-line plots of log K(M(R-PO3))M versus pK(H(R-PO3)H for simple phosph(on)ate ligands. R-PO3(2-), where R represents a non-inhibiting residue without an affinity for metal ions, proves that the primary binding site of (Dien)Pt(PMEA-N1) is the phosphonate group with all metal ions studied; in fact, Mg2+, Ca2+ and Ni2+ coordinate (within the error limits) only to this site. For the Cu[(Dien)Pt(PMEA-N1)]2+ and Zn[(Dien)Pt(PMEA-N1)]2- systems also the formation of five-membered chelates involving the ether oxygen of the -CH2-O-CH2-PO3(2-) residue could be detected; the formation degrees are about 60% and 30%, respectively. The metal-ion-binding properties of the isomeric (Dien)Pt(PMEA-N7) species studied previously differ in so far that the resulting M[(Dien)Pt(PMEA-N7)]2+ complexes are somewhat less stable, but again Cu2+ and Zn2+ also form with this ligand comparable amounts of the mentioned five-membered chelates. In contrast, both M[(Dien)Pt(PMEA-N1/N7)]2+ complexes differ from the parent M(PMEA) complexes considerably; in the latter instance the formation of the five-membered chelates is of significance for all divalent metal ions studied. The observation that divalent metal-ion binding to the phosphonate group of (Dien)Pt(PMEA-N1) and (Dien)Pt(PMEA-N7) is only moderately inhibited (about 0.2-0.4 log units) by the twofold positively charged (Dien)Pt2+ unit at the adenine residue allows the general conclusion, considering that PMEA is a nucleotide analogue, that this is also true for nucleotides and that consequently participation of, for example, two metal ions in an enzymatic process involving nucleotides is not seriously hampered by charge repulsion.

Adenine↗
PubMed2001

Comparative studies on the certification of reference materials by ICPMS and TIMS using isotope dilution procedures.

A comparison of different isotope dilution mass spectrometric (IDMS) procedures using inductively coupled plasma mass spectrometry (ICPMS) and thermal ionization mass spectrometry (TIMS) was carried out to examine the degree of equivalence between the used procedures in terms of requirements for reference material certification. The comparison was based on the measurement results and their uncertainties. The sample used in this study is a pure zinc metal to be certified by the Bureau Communie de Référence (BCR) for amount contents of different trace elements. This study focuses on cadmium and thallium. The TIMS values contributed to the certified values. To guarantee identical conditions as far as possible for the procedures under investigation, the samples were split into subsamples after spiking and digestion took place. Thus, every IDMS procedure started with an identical set of samples. In total, four different IDMS procedures and one external calibration procedure using internal standardization as an example of routine analysis were applied. The IDMS procedures divide in a group with and a group without trace/matrix separation. Multicollector TIMS (TI-MC-MS) and multicollector ICPMS (ICP-MC-MS) were used in combination with trace/matrix separation, whereas quadrupole ICPMS (ICP-QMS) and ICP-MC-MS were also applied to nonseparated samples. All IDMS results agree well within their combined uncertainties, while some results from the external calibration procedure do not. IDMS results obtained by ICPMS without separation are comparable to those obtained by TI-MC-MS with separation regarding precision and accuracy. The smallest uncertainties were achieved using ICP-MC-MS in combination with trace/matrix separation.

Journal Article↗
PubMed2001

Enterobactin: the characteristic catecholate siderophore of Enterobacteriaceae is produced by Streptomyces species.(1).

Enterobactin is described in the literature as the typical iron-chelating compound (siderophore) produced by bacteria of the family Enterobacteriaceae. In the course of a HPLC with diode array detection screening programme for detection of novel secondary metabolites, enterobactin, its biosynthetic precursor 2,3-dihydroxy-N-benzoylserine and its linear dimer and trimer condensation products were found to be produced by two Streptomyces strains besides the trihydroxamate-type siderophores desferri-ferrioxamine B and E.

Chromatography, High Pressure Liquid↗
PubMed2001

Phase-field modeling of stress-induced instabilities.

A phase-field approach describing the dynamics of a strained solid in contact with its melt is developed. Using a formulation that is independent of the state of reference chosen for the displacement field, we write down the elastic energy in an unambiguous fashion, thus obtaining an entire class of models. According to the choice of reference state, the particular model emerging from this class will become equivalent to one of the two independently constructed models on which brief accounts have been given recently [J. Müller and M. Grant, Phys. Rev. Lett. 82, 1736 (1999); K. Kassner and C. Misbah, Europhys. Lett. 46, 217 (1999)]. We show that our phase-field approach recovers the sharp-interface limit corresponding to the continuum model equations describing the Asaro-Tiller-Grinfeld instability. Moreover, we use our model to derive hitherto unknown sharp-interface equations for a situation including a field of body forces. The numerical utility of the phase-field approach is demonstrated by reproducing some known results and by comparison with a sharp-interface simulation. We then proceed to investigate the dynamics of extended systems within the phase-field model which contains an inherent lower length cutoff, thus avoiding cusp singularities. It is found that a periodic array of grooves generically evolves into a superstructure which arises from a series of imperfect period doublings. For wave numbers close to the fastest-growing mode of the linear instability, the first period doubling can be obtained analytically. Both the dynamics of an initially periodic array and a random initial structure can be described as a coarsening process with winning grooves temporarily accelerating whereas losing ones decelerate and even reverse their direction of motion. In the absence of gravity, the end state of a laterally finite system is a single groove growing at constant velocity, as long as no secondary instabilities arise (that we have not been able to see with our code). With gravity, several grooves are possible, all of which are bound to stop eventually. A laterally infinite system approaches a scaling state in the absence of gravity and probably with gravity, too.

Journal Article↗
PubMed2001

The crystal structure of the ttCsaA protein: an export-related chaperone from Thermus thermophilus.

The CsaA protein was first characterized in Bacillus subtilis as a molecular chaperone with export-related activities. Here we report the 2.0 Angstrom-resolution crystal structure of the Thermus thermophilus CsaA protein, designated ttCsaA. Atomic structure and experiments in solution revealed a homodimer as the functional unit. The structure of the ttCsaA monomer is reminiscent of the well known oligonucleotide-binding fold, with the addition of extensions at the N- and C-termini that form an extensive dimer interface. The two identical, large, hydrophobic cavities on the protein surface are likely to constitute the substrate binding sites. The CsaA proteins share essential sequence similarity with the tRNA-binding protein Trbp111. Structure-based sequence analysis suggests a close structural resemblance between these proteins, which may extend to the architecture of the binding sites at the atomic level. These results raise the intriguing possibility that CsaA proteins possess a second, tRNA-binding activity in addition to their export-related function.

Amino Acid Sequence↗
PubMed2001

p53 and Ki-67 as predictive markers for radiosensitivity in squamous cell carcinoma of the oral cavity? an immunohistochemical and clinicopathologic study.

PURPOSE: Previously published data relating the expression of p53 and Ki-67 to radiation response in head and neck cancer are conflicting. This may be due to differences in patient selection and treatment modalities. In this study of a homogenous population of patients with oral cavity cancer, Ki-67 and p53 indices were correlated with histopathologically assessed tumor regression after preoperative radiochemotherapy and longterm outcome. METHODS AND MATERIALS: Eighty-eight patients with squamous cell carcinoma of the oral cavity and treated between September 1985 and November 1995 by preoperative radiochemotherapy and definitive surgery were included in this analysis. By immunohistochemistry (IHC) the pre-irradiation expression of p53 and of Ki-67 were analyzed and correlated with the histopathologically proven tumor regression, overall survival and local control. RESULTS: The overall 2- and 5-year survival rates were 76.5% and 63%, the locoregional control rates were 84% and 79%, respectively. After preoperative radiochemotherapy 29 patients (33%) showed complete tumor regression (ypT(0) classification). Survival and local control rates were significantly higher for patients showing ypT(0) classification than ypT(1-4) classification (p < 0.01). This effect was independent of pretreatment tumor classification in multivariate analysis. Pre-irradiation p53 status and Ki-67 index had no influence on tumor regression and clinical outcome in these patients. CONCLUSION: Complete tumor regression after preoperative treatment is related to an improved outcome in combined modality treatment of oral cavity cancer. The presented study could not demonstrate an influence of p53 and Ki-67 status as detected by immunohistochemical staining on survival, local control, or tumor regression after radiochemotherapy.

Adult↗