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Biomedical subjects

M Westphal

Publications and source records attributed to M Westphal.

16 recordsLinked to original sources

Treatment of tumours of the pineal region and posterior part of the third ventricle.

The evaluation of tumours located in the posterior part of the third ventricle or pineal region is achieved best by magnet resonance imaging (MRI). It shows the exact localization and extent, the involvement of neighbouring structures like thalamus or quadrigeminal plate and the displacement of the large veins, the internal cerebral veins, the vein of Galen and the veins of Rosenthal. If only CT is available, angiography should be performed prior to operation to identify the course of the veins. In children with a pineal region tumour the "tumour markers" AFP and beta-HCG should be determined before operation. We approach the rare tumours entirely located within the posterior part of the third ventricle by the posterior interhemispheric transcallosal route with the patient in prone position with the head elevated. The same approach is used for pineal region tumours extending above the internal cerebral veins. Tumours arising from the posterior thalamus extending into the thalamus and ventricle as well, are better approached by the posterior transcortical transventricular route since the lateral view is rather limited by the midline approach. The most frequent tumours in the pineal region are approached if they are located below the internal veins by the infratentorial, supracerebellar route in the sitting position. A total of 60 cases are evaluated. If AFP and/or beta-HCG are positive a highly malignant nongerminomatous germ-cell tumour must be suspected. We recommend initial chemotherapy with a combination of Vinblastine, Ifosfamide and Cis-platin without biopsy to avoid tumour seeding. After the "markers" are normalized operative removal of the residual tumour and radiotherapy should be carried out. In a series of 13 children operated on for pineal region tumours a rigid neuropsychological and endocrine evaluation was performed with encouraging results. During the last 10 years we have performed 49 open operations and 11 stereotactic biopsies. 40% of the patients were children under the age of 18. 40% of the tumours in childhood and 60% in adults were benign. In childhood 24% were germinomas and 20% non-germinomatous germ cell tumours.

Adult

Receptors for platelet derived growth factor in human glioma cell lines and influence of suramin on cell proliferation.

A panel of 11 established human glioma cell lines was used to evaluate PDGF receptor binding using radioiodinated biosynthetic PDGF-AA and PDGF-AB as primary ligands. It was found that PDGF-receptor-binding was qualitatively heterogeneous. The affinities for PDGF-AA as well as PDGF-AB binding were within a close range of 0.13-0.33 nM and 0.16-1.1 nM, respectively. The number of binding sites per cell ranged between 56.000 and 250.000 for PDGF-AA and 72.000 to 300.000 for PDGF-AB. Two lines had only background levels of PDGF-AA binding. PDGF-AB binding was the dominant binding component in all but one cell line. In seven cell lines there were two binding components upon saturation analysis consisting of a high affinity component and a non-saturable low affinity component. PDGF and PDGF-receptors are suspected to be part of an autocrine loop in gliomas. Therefore, the effect of suramin on cell proliferation in serumfree cultures was tested in the same cell lines using doses of 25,200 or 500 micrograms/ml. It was found that the response to suramin was variable and that two cell lines still reached 2.8 fold and 4.5 fold their initial cell density even in the presence of 500 micrograms/ml whereas all other cells were completely arrested. Analyzing the response to 200 micrograms/ml it became evident, that the PDGF binding characteristics are of no reliable predictive value in respect to the efficacy of suramin.

Brain Neoplasms

Primary spinal malignant schwannoma: clinical, histological and cytogenetic findings.

Of the 19 patients who presented between 1980 and 1990 to the Department of Neurosurgery, University of Hamburg, F. R. G. with malignant schwannoma, 5 patients suffered from primary malignant spinal schwannoma (mean age 44 years, only one patient with von Recklinghausen's disease). Here we report the clinical, histological, and cytogenetic features of the five cases with primary malignant spinal schwannoma and discuss the prognostic aspects of this rare tumor.

Adolescent

Antigenic staining patterns of human glioma cultures: primary cultures, long-term cultures and cell lines.

The immunocytochemical staining patterns of cultured glioma cells were investigated. Fifty nine individual cases were stained at different in vitro ages for glial fibrillary acidic protein, fibronectin, galactocerebroside, HNK-1/Leu 7, A2B5, vimentin, factor VIII and A4. Histologically, the cases were composed of eight low-grade astrocytomas, 11 high-grade astrocytomas, four low-grade oligodendrogliomas, seven high-grade oligodendrogliomas and 29 glioblastomas. The 45 cases were analysed within the first 3 weeks of culture, many of them as primary cultures. In 11 cases stainings were performed repeatedly at intervals of up to 6 months. Glial fibrillary acidic protein staining was positive in most of the early cultures of astrocytomas (low and high grade) and glioblastomas; expression in more than 50% of the cells was found in 1 of 5 low-grade astrocytomas, 5 of 11 high-grade astrocytomas and 14 of 29 glioblastomas. Two of the high-grade astrocytomas were stained once more after 6 weeks in culture and were found to be only 1% positive for glial fibrillary acidic protein but strongly positive for fibronectin. The same was true for five of the glioblastoma cases. Two of these cases remained glial fibrillary acid protein positive and developed into stable permanent cell lines. Only one case started with 1% of glial fibrillary acidic protein positive cells and later developed into a 99% glial fibrillary acidic protein positive cell line. Neither HNK-1/Leu 7 expression nor A2B5 staining appeared to have a relationship to the glial fibrillary acidic protein staining. It was observed that glial fibrillary acidic protein and HNK-1/Leu 7 were both 100% in some cases but that later one of the two antigens disappeared but not the other. The amount of glial fibrillary acidic protein staining does not allow the prediction of A2B5 staining. The study shows that initiation of primary cultures on an extracellular matrix yields more glial fibrillary acidic protein positive cells in primary cultures than have been found in other studies. It is concluded that only a rigid standardization of culture conditions will ensure the validity of comparisons of in vitro data obtained in primary cultures.

Antigens, Neoplasm

Expandable tubular stents for treatment of arterial occlusive diseases: experimental and clinical results. Work in progress.

The balloon-expandable vascular prosthesis consists of a flexible, knitted tantalum wire mesh tube. To demonstrate its pliability, this prosthesis was tested experimentally in 10 mongrel dogs by implanting it into the proximal femoral arteries. The maximum follow-up time was 1 year. On the basis of the experimental results, in which there was no relevant stenosis, occlusion, or migration of the vascular prosthesis, nine patients were treated: one with iliac artery occlusive disease and eight with superficial femoral artery (SFA) occlusive disease (four reocclusions after angioplasty and four unsatisfactory primary angioplasty results). One SFA lesion was treated with the crossover method from the contralateral side. All implants remained patent without hemodynamically significant stenoses, with the longest observation time being 6 months. Flexible, expandable vascular prostheses are promising adjuncts to angioplasty.

Aged

Changes in average length of stay and average charges generated following institution of PSRO review.

A five-year review of accounting data at a university hospital shows that immediately following institution of concurrent PSRO admission and length of stay review of Medicare-Medicaid patients, there was a significant decrease in length of stay and a fall in average charges generated per patient against the inflationary trend. Similar changes did not occur for the non-Medicare-Medicaid patients who were not reviewed. The observed changes occurred even though the review procedure rarely resulted in the denial of services to patients, suggesting an indirect effect of review.

Accounting

Patterns of integration of viral DNA sequences in the genomes of adenovirus type 12-transformed hamster cells.

The patterns of integration of the viral genome have been analyzed in four hamster cell lines transformed by adenovirus type 12 (Ad12). It has previously been shown that in each of the cell lines HA12/7, T637, A2497-2 and A2497-3, the viral genome persists in multiple copies, and that different parts of the viral DNA are represented non-stoichiometrically (Fanning and Doerfler, 1976). All four cell lines are oncogenic when injected into hamsters. The DNA from each of the cell lines was extracted and cleaved in different experiments with restriction endonucleases Bam HI, Bgl II, Eco RI, Hind III, Hpa II or Sma I. The DNA fragments were separated on 1% agarose slab gels and transferred to nitrocellulose filters by the Southern technique. Ad12 DNA sequences were detected by hybridization to Ad12 DNA, which was 32 P-labeled by nick translation, and by subsequent autoradiography. In some experiments, the 32P-labeled Eco RI restriction endonuclease fragments of Ad12 DNA were used to investigate the distribution of specific segments of the viral genome in the cellular DNA. For each cell line, a distinct and specific pattern of integrated viral DNA sequences is observed for each of the restriction endonucleases used. Moreover, viral sequences complementary to the isolated Eco RI restriction endonuclease fragments are also distributed in patterns specific for each cell line. There are striking differences in integration patterns among the four different lines; there are also similarities. Because the organization of cellular genes in virus-transformed as compared to normal cells has not yet been determined, conclusions about the existence or absence of specific integration sites for adenovirus DNA appear premature. Analysis of the integration patterns of Ad12 DNA in the four hamster lines investigated reveals that some of the viral DNA molecules are fragmented prior to or during integration. Analysis with specific restriction endonuclease fragments demonstrates that the Eco RI B, D and E fragments, comprising a contiguous segment from 0.17-0.62 fractional length units of the viral DNA, remain intact during integration in a portion of the viral DNA molecules. Although each cell line carries multiple copies of Ad12 DNA, the viral DNA sequences are concentrated in a small number of distinct size classes of fragments. This finding is compatible with, but does not prove, the notion that at least a portion of the viral DNA sequences, is integrated into repetitive sequences, or else that the integrated viral sequences have been amplified after integration. In the three cell lines which were tested, the integration pattern is stable over many generations, with continuous passage-twice weekly-of cells for 6-7 months. In the three cell lines which were examined, the integration pattern is identical in a number of randomly isolated clones. Hence it can be concluded that the patterns of integration are identical among all cells in a population of a given line of transformed cells.

Adenoviruses, Human

Integration of clinical and academic nursing at the hospital clinical unit level.

In a successful attempt to solve problems in Pediatric Nursing at the Medical University of South Carolina, a Department Chairman was named Director-Chairman of Pediatric Nursing and given operational authority over both clinical and academic nursing in Pediatrics. The results were more efficient administration, a higher quality of patient care and an enriched environment for student learning.

Curriculum

Transcription of the genome of adenovirus type 12. III. Maps of stable RNA from productively infected human cells and abortively infected and transformed hamster cells.

The adenovirus type 12-specific mRNA and the stable nuclear RNA from productively infected KB cells, early postinfection, from abortively infected BHK-21 cells, and from the adenovirus type 12-transformed hamster lines T637 and HA12/7 have been mapped on the genome of adenovirus type 12. The intact separated heavy (H) and light (L) strands of adenovirus type 12 DNA have been used to determine the extent of complementarity of the mRNA or nuclear RNA from different cell lines to each of the strands. More precise map positions have been obtained by the use of the H and L complements of the fragments of adenovirus type 12 DNA which were produced with the EcoRI and BamHI restriction endonucleases. The results of the mapping experiments demonstrate that the mRNA's isolated early from productively and abortively infected and from two lines of transformed cells are derived from the same or similar regions of the adenovirus type 12 genome. The map positions on the adenovirus type 12 genome for the mRNA from the cell lines as indicated correspond to regions located approximately between 0 and 0.1 and 0.74 and 0.88 fractional length units on the L strand and to regions between 0.63 and 0.74 and 0.89 and 1.0 fractional length units on the H strand. The HA12/7 line lacks mRNA complementary to the region between 0.74 and 0.88 fractional length units on the L strand. Similar data are found for the nuclear RNA, except that the regions transcribed are more extensive than those observed in mRNA. The polarity of the H strand has its 3'-end on the right terminus in the EcoRI A fragment, and the L strand has its 3'-end on the left terminus in the EcoRI C fragment. Thus, the H strand is transcribed from right to left (1 = leftward strand); and the L strand is transcribed from left to right (r = rightward strand). The designations H and L refer to the relative heavy and light densities of the two strands in polyuridylic-polyguanylic acid-CsCl density gradients. The EcoRI C-H and D-H complements have been shown to be part of the intact L strand; thus, there is a "reversal in heaviness" on the left terminus of the viral DNA.

Adenoviruses, Human

Coordinated incorporation of nascent peptidoglycan and teichoic acid into pneumococcal cell walls and conservation of peptidoglycan during growth.

Choline-containing pneumococcal cell wals are sensitive to autolysin, whereas ethanolamine-containing walls are not. Bacteria were labeled with radioactive peptidoglycan precursors while growing either in choline- or in ethanolaminecontaining media. Subsequently, the labeled cells were allowed to grow for four to five generations in nonradioactive medium supplemented with the alternative amino alcohol source (i.e. cells labeled in choline medium yields ethanolamine; cells labeled in ethanolamine medium yields choline). The autolysin sensitivity of the isotope label in cell walls prepared from such bacteria indicates that nascent peptidoglycan and teichoic acid units that are synthesized at the same time are attached to one another, incorporated into the cell surface at the cellular equator, and remain conserved during growth the division of the bacteria.

Alanine

On the physiological functions of teichoic acids.

The choline-containing teichoic acids of pneumococci can be modified by biosynthetic replacement of the choline residues with certain structural analogues, such as ethanolamine (EA) or the N-monomethyl-(MEA) and N-dimethyl-(DEA) amino derivatives of ethanolamine. Cells containing such analogues in their teichoic acids develop pleiomorphic alterations in several physiological properties, which include resistance to detergent-induced lysis and inhibition of cell separation (chain formation). We report here the results of physiological studies on the mechanism of these two phenomena. Our results are summarized in the following: (a) Pneumococci grown on various amino alcohols produce cell walls of identical amino sugar and amino acid composition. (b) Both choline- and EA-containing teichoic acids seem to follow the same conservative pattern of segregation during growth and cell division.(c)Lysis sensitivity of pneumococci requires the juxtaposition oflysissensitive (choline-containing) cell walls and endogenous autolysin at the cell wall growth zone. (d) Upon readdition of choline to ethanolamine-containing cells, lysis sensitivity and catalytically active (C-type) autolysin reappear in the bacteria with the same kinetics. (e) The chains of EA-grown pneumococci contain fully compartmentalized cells and normal cross walls.

Amino Alcohols

Structure and composition of the adenovirus type 2 core.

The structure and composition of the core of adenovirus type 2 were analyzed by electron microscopy and biochemical techniques after differential degradation of the virion by heat, by pyridine, or by sarcosyl treatment. In negatively stained preparations purified sarcosyl cores reveal spherical subunits of 21.6-nm diameter in the electron microscope. It is suggested that these subunits are organized as an icosahedron which has its axes of symmetry coincident with those of the viral capsid. The subunits are connected by the viral DNA molecule. The sarcosyl cores contain the viral DNA and predominantly the arginine/alanine-rich core polypeptide VII. When sarcosyl cores are spread on a protein film, tightly coiled particles are observed which gradually unfold giving rise to a rosette-like pattern due to the uncoiling DNA molecule. Completely unfolded DNA molecules are circular. Pyridine cores consist of the viral DNA and polypeptides V and VII. In negatively stained preparations of pyridine cores the subunit arrangement apparent in the sarcosyl cores is masked by an additional shell which is probably formed by polypeptide V. In freeze-cleaved preparations of the adenovirion two fracture planes can be recognized. One fracture plane probably passes between the outer capsid of the virion and polypeptide V exposing a subviral particle which corresponds to the pyridine core. The second fracture plane observed could be located between polypeptide V and the polypeptide VII-DNA complex, thus uncovering a subviral structure which corresponds to the sarcosyl core. In the sarcosyl core polypeptide VII is tightly bound to the viral DNA which is susceptible to digestion with DNase. The restriction endonuclease EcoRI cleaves the viral DNA in the sarcosyl cores into the six specific fragments. These fragments can be resolved on polyacrylamide-agarose gels provided the sarcosyl cores are treated with pronase after incubation with the restriction endonuclease. When pronase digestion is omitted, a complex of the terminal EcoRI fragments adenovirus DNA and protein can be isolated. From this complex the terminal DNA fragments can be liberated after pronase treatment. The complex described is presumably responsible for the circularization of the viral DNA inside the virion. The nature of the protein(s) involved in circle formation has not yet been elucidated.

Adenoviridae