Biomedical subjects

R Kerschmann

Publications and source records attributed to R Kerschmann.

10 recordsLinked to original sources

PubMed1995

Chromosome-9 loss detected by fluorescence in situ hybridization in bladder cancer.

A loss of chromosome-9 material is one of the most frequent genomic aberrations known in bladder cancer. In order to better understand the role of chromosome-9 losses in bladder cancer, 125 formalin-fixed and 37 unfixed bladder tumors were examined using fluorescence in situ hybridization (FISH). A repetitive probe for a pericentromeric region on 9q12 (pHUR98) was applied for chromosome-9 copy-number enumeration. Under-representation of chromosome 9 was found in 74 of 162 cases. There was no association between loss of chromosome 9 and increased grade or stage, papillary growth pattern, p53 protein expression, or tumor-cell proliferation (Ki-67). These data show that chromosome-9 loss is an early event in bladder-cancer development, occurring independently of p53 alterations. In order to determine the prevalence of large sub-regional chromosome-9 deletions, dual hybridizations with pHUR98 and cosmid probes for 9q34, 9q22, and 9p21 were performed. Partial deletion was detected in only 1 of 36 cases for 9q34 and in 1 of 24 cases for 9p21. Surprisingly, amplification of the interferon alpha locus on 9p21 was seen in 1 of 24 tumors. The finding of 9p amplification may indicate the site of an oncogene relevant for bladder cancer.

Chromosome Deletion↗

PubMed1995

Identification of gains and losses of DNA sequences in primary bladder cancer by comparative genomic hybridization.

Comparative genomic hybridization (CGH) makes it possible to detect losses and gains of DNA sequences along all chromosomes in a tumor specimen based on the hybridization of differentially labeled tumor and normal DNA to normal human metaphase chromosomes. In this study, CGH analysis was applied to the identification of genomic imbalances in 26 bladder cancers in order to gain information on the genetic events underlying the development and progression of this malignancy. Losses affecting 11p, 11q, 8p, 9, 17p, 3p, and 12q were all seen in more than 20% of the tumors. The minimal common region of loss in each chromosome was identified based on the analysis of overlapping deletions in different tumors. Gains of DNA sequences were most often found at chromosomal regions distinct from the locations of currently known oncogenes. The bands involved in more than 10% of the tumors were 8q21, 13q21-q34, 1q31, 3q24-q26, and 1p22. In conclusion, these CGH data highlight several previously unreported genetic alterations in bladder cancer. Further detailed studies of these regions with specific molecular genetic techniques may lead to the identification of tumor suppressor genes and oncogenes that play an important role in bladder tumorigenesis.

Chromosome Mapping↗

PubMed1995

c-myc copy number gains in bladder cancer detected by fluorescence in situ hybridization.

Amplification and overexpression of c-myc have been suggested as prognostic markers in human cancer. To assess the role of c-myc gene copy number alterations in bladder cancer, 87 bladder tumors were examined for c-myc aberrations by fluorescence in situ hybridization. Dual labeling hybridization with a repetitive pericentromeric probe specific for chromosome 8 and a probe for the c-myc locus (at 8q24) was performed to analyze c-myc copy number in relation to chromosome 8 copy number on a cell by cell basis. A clear-cut c-myc amplification (up to 40 to 150 copies per cell) was found in 3 tumors. There was a low level c-myc copy number increase in 32 of the remaining 84 tumors. There was no association of low level c-myc copy number increase with c-myc protein overexpression. This suggests that a c-myc gene copy number gain as detected by fluorescence in situ hybridization does not necessarily reflect a disturbed c-myc gene function but may indicate a structural chromosome 8 abnormality including gain of distal 8q. The strong association of low level c-myc (8q) gains with tumor grade (P < 0.0001), stage (P < 0.0001), chromosome polysomy (P < 0.0001), p53 protein expression (P = 0.0019), p53 deletion (P = 0.0403), and tumor cell proliferation (Ki67 labeling index; P = 0.0021) is consistent with a role of chromosome 8 alterations in bladder cancer progression.

Chromosomes, Human, Pair 8↗

PubMed1994

S-100 protein-negative malignant melanoma: fact or fiction? A light-microscopic and immunohistochemical study.

S-100 protein is considered a characteristic immunohistochemical marker for all nevomelanocytic lesions, in which it is expected to be present consistently. We reviewed 17 cases of malignant melanomas that previously tested negative for S-100 protein. They were reevaluated by light microscopy, a broad panel of immunohistochemical reagents including monoclonal and polyclonal antibodies to S-100 protein, and electron microscopy. On reexamination, five of the 17 cases were reclassified as non-melanoma tumors, and eight of the 17 cases were found to be positive for S-100 protein (six with monoclonal and eight with polyclonal antibodies) and HMB-45 antigen, consistent with melanoma. The remaining four cases repeatedly tested negative for S-100 protein despite various antigen enhancement methods, but they were positive for HMB-45 antigen and contained premelanosomes or melanosome-like structures by electron microscopy. Two of these repeatedly S-100 negative melanomas were acrally located; although the numbers are small, a possible relationship to a specific anatomic location cannot be excluded. These findings suggest that in a small subset of melanomas S-100 protein is either not fully expressed or is below the level that can be detected by routine immunohistochemistry. We also conclude that in the majority of the initially S-100-negative cases of melanomas, the misdiagnosis may occur due to the use of an incomplete immunohistochemical panel, technical reasons, or the inherent variability of tissue expression of S-100 protein.

Antigens, Neoplasm↗

PubMed1991

Centromeric copy number of chromosome 7 is strongly correlated with tumor grade and labeling index in human bladder cancer.

The relationship between interphase cytogenetics and tumor grade, stage, and proliferative activity was investigated in 27 transitional cell carcinomas of the urinary bladder. Using fluorescence in situ hybridization with chromosome-specific DNA probes, the copy number of pericentromeric sequences on chromosomes 7, 9, and 11 was detected within interphase nuclei in touch preparations from tumor biopsies. Monosomy of chromosome 9 was detected in 9 of 22 cases (41%), while tetrasomy for chromosomes 7 and 11 was detected in 10 of 26 (38%) and 6 of 23 (26%) cases, respectively. Copy number of chromosome 7 was the most highly correlated with increasing tumor grade (r2 = 0.616, P less than 0.001, Spearman rank correlation) or increasing pathological stage (r2 = 0.356, P less than 0.002). Copy number for chromosome 9 did not correlate with either grade or stage (P greater than 0.05). Tumor labeling index (LI) was determined after in vitro 5-bromodeoxyuridine incorporation, while proliferating cell nuclear antigen LI was determined immunohistochemically. Increasing LI by either method correlated with increasing copy number for all three chromosomes tested (r2 = 0.473, P less than 0.002 for 7; r2 = 0.384, P less than 0.01 for 11; and r2 = 0.316, P less than 0.05 for 9). Since high tumor grade, stage, and LI are all indicative of more aggressive tumor behavior and worse prognosis, these findings suggest that polysomy, especially for chromosome 7, may be highly predictive for bladder tumor aggressiveness.

Aged↗

PubMed1988

Streptomycin in the chick embryo: post-hatching vestibular behavior and morphology.

Developing chick embryos were exposed to streptomycin injected on days 5 through 13 of the 21 day developmental period. Histological and behavioral abnormalities were found almost exclusively in chicks exposed after day 7. The nature of the behavioral deficits included abnormal head posture, head tremor, and inability to compensate for applied vestibular stimuli. Head movement measurements showed that the head tremor had frequencies of oscillations from 10-35 Hz. The amplitude of the tremor was a large as 10 degrees. Histology showed damage to the secretory dark cells of the membranous labyrinth in those chicks that showed behavior changes. Even with increased dosages chicks exposed prior to day 7 rarely showed abnormal vestibular behavior but instead experienced increased mortality. Further tests examining tissue levels of streptomycin showed little or no streptomycin in embryos until day 10. These results are discussed in terms of their utility as an alternative model to surgical manipulation of the vestibular system in developing embryos. Behavioral consequences are compared to other work with drugs and to the effects of weightlessness and unusual environments on vestibular orientation and behavior.

Animals↗

PubMed1986

Effect of dye laser pulse duration on selective cutaneous vascular injury.

The pulsed dye laser at 577 nm, a wavelength well absorbed by oxyhemoglobin, causes highly selective thermal injury to cutaneous blood vessels. Confinement of thermal damage to microvessels is, in theory, related to the laser exposure time (pulsewidth) on selective vascular injury. This study investigates the effect of 577 nm dye laser pulsewidth on selective vascular injury. Nine Caucasian, normal volunteers received 577 nm dye laser exposures at pulsewidths of 1.5-350 microseconds to their skin. Clinical purpura threshold exposure doses were determined in each volunteer, and biopsies of threshold and suprathreshold doses were examined in each volunteer. The laser exposure dose required to produce purpura increased as pulsewidth increased in all 9 subjects (p less than 0.001). This finding corresponds to laser pulsewidths equal to or exceeding the thermal relaxation times for dermal blood vessels. Histologically, vessel damage was selectively, but qualitatively, different for short vs long pulsewidths. Pulsewidths shorter than 20 microseconds caused vessel wall fragmentation and hemorrhage, whereas longer pulsewidths caused no significant hemorrhage. The purpura noted clinically appears to be due to a coagulum of intralumenal denatured erythrocytes. At 24 h, there was marked vessel wall necrosis at all pulsewidths. The short pulsewidths may cause erythrocyte vaporization, rapid thermal expansion, and mechanical vessel rupture with hemorrhage. Long pulsewidths appear to cause thermal denaturation with less mechanical vessel damage. The selective, nonhemorrhagic, vascular necrosis caused by the long-pulsewidth dye laser may lead to a more desirable clinical outcome in the therapy of blood vessel disease processes.

Capillary Permeability↗

PubMed1985

Effect of skin temperature on selective vascular injury caused by pulsed laser irradiation.

The effect of skin temperature on vascular-specific injury caused by pulsed laser irradiation was examined. Ten healthy human volunteers were exposed to 1.5 microsecond pulses from a dye laser tuned to 577 nm. Compared to normothermic conditions (33 degrees C skin temperature) significantly more laser energy (p less than 0.01) was required to produce grossly visible purpura when the skin was cooled to 20 degrees C or heated to 40 degrees C. Histologically, laser-induced damage was confined to blood vessels at all three skin temperatures studied. At purpura threshold dose, there was intravascular agglutination without extravasation of red blood cells at 20 degrees C whereas at 33 degrees and 40 degrees C there was extravasation of red blood cells.

Adolescent↗

PubMed1984

The effect of epidermal pigmentation on selective vascular effects of pulsed laser.

The effect of epidermal pigmentation on the threshold exposure dose for inducing purpura with a tunable dye laser at 577 nm, 1.5 microseconds pulse duration, was studied in 21 human volunteers with varied genetically determined amounts of melanin. More laser energy was required to produce purpura as constitutive skin pigmentation increased. Histology showed that, in lighter skin, the laser threshold dose produced the most specific vascular injury with no disruption of surrounding structures. In more pigmented skin, damage occurred in the epidermal basal layer and very few changes were seen in blood vessels below.

Adolescent↗

PubMedDate not supplied

Normal vestibular function in chicks after partial exposure to microgravity during development.

Sixty-four fertilized chicken eggs, half at developmental Day 2 and half at Day 9, were exposed to micro-gravity for 5 days aboard the shuttle. Postflight examination showed that none of the Day 2 flight embryos had survived, whereas the Day 9 flight group and both groups of synchronous ground control embryos appeared viable. One-half of the Day 9 flight and ground control embryos were dissected and the temporal bones preserved in acetone for morphological examination. The other half was allowed to hatch to examine vestibularly related behavioral changes. Morphology of the lagenar otoconia was evaluated by scanning electron microscopy. Behavioral changes were accessed by a battery of reflex tests and recordings of spontaneous and vestibularly driven head movements. The results from both the morphological and behavioral studies showed no consistent difference between the flight and the control animals. Several hypotheses may account for this negative result. Because all the Day 2 embryos failed to survive, the remaining Day 9 chicks may have passed the critical developmental period of the chick's vestibular system. Also, the reexposure of the developing chick embryo to earth's 1-g environment may have masked any adverse behavioral effects that exposure to Microgravity may have caused.

Animals↗