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Biomedical subjects

J Kramer

Publications and source records attributed to J Kramer.

At least 19 recordsLinked to original sources

Molecular cloning, analysis, and chromosomal localization of a mouse genomic sequence related to the human papillomavirus type 18 E5 region.

The E5 open reading frame (ORF) from bovine papillomavirus type 1 (BPV 1) as well as the E5 ORFs from human papillomaviruses (HPV) type 6 and type 16 have been reported to transform immortalized rodent cells. In an analysis of murine and human tumors for the presence of putative papillomavirus-related sequences, we cloned amplified cellular sequences from the mouse cell line Eb that cross-hybridized with the E5 ORF of HPV 18. A 2.1-kb fragment termed HC1 was sequenced. In normal murine cells, it was present as a single-copy genomic sequence located on chromosome 8. A region of 213 nucleotides corresponded to the E5 gene (HC1 E5), based on the best alignments and on the presence of direct and inverted repeats bearing a central sequence motif. These structural elements are also present in the HPV 18 E5 ORF. HC1 E5 contained an ORF that was transcribed bidirectionally. The transcription in the E5 direction was enhanced in RNA obtained from organs and tumors from carcinogen-treated animals and C127 cells. The polypeptide deduced from the sequence was related to E5 proteins from genital papillomaviruses, to the putative product of the Q300 mouse gene, and to several viral and human growth factors. The data suggest that there may be several cellular counterparts to the viral E5 proteins.

Amino Acid Sequence

MRI of cartilaginous tumours of the larynx.

Cartilaginous lesions of the larynx are uncommon, approximately 250 cases being documented in the literature. In general, these tumours grow slowly, exhibiting only local aggressiveness. Distant metastases are rare. Up until now CT has been the best diagnostic tool for the evaluation of these tumours because it demonstrates intratumoral calcification so well. To the best of our knowledge there are no reports of the use of MRI for these lesions. Three cases of cartilaginous laryngeal tumours are presented, emphasizing the MRI features.

Cartilage Diseases

C1 inhibitor hinge region mutations produce dysfunction by different mechanisms.

Heterozygosity for a mutant dysfunctional C1 inhibitor protein, a member of the serine proteinase inhibitor (serpin) superfamily, results in type II hereditary angioneurotic oedema. We identified a "hinge" region mutation in C1 inhibitor with a Val to Glu replacement at P14 Val-432. Recombinant C1 inhibitors P10 Ala-->Thr and P14Val-->Glu did not form stable complexes with fluid phase C1s or kallikrein. The P14 Val-->Glu mutant, however, was cleaved to a 96K form by C1s, while the P10 Ala-->Thr mutant was not. The recombinant P10 mutant also did not complex with C1s, kallikrein or beta-factor Xlla-Sepharose. The two mutations, therefore, result in dysfunction by different mechanisms: in one (P14 Val-->Glu), the inhibitor is converted to a substrate, while in the other (P10 Ala-->Thr), interaction with target protease is blocked.

Alanine

Factors influencing the DNA content of radiation-induced micronuclei.

The distribution of the DNA content of radiation-induced micronuclei was analysed in several cell lines (Chinese hamster, Syrian hamster and mouse NIH-3T3 cells) by flow cytometry. Frequency and DNA content of micronuclei were measured simultaneously using fluorescence and forward scatter signals of micronuclei and nuclei in suspension stained with ethidium bromide. Computerized random breakage of chromosomes and random combination of fragments was performed to compare the measured micronucleus distributions in synchronized cells irradiated during G1-phase with calculated distributions. The measured DNA distribution of radiation-induced micronuclei was found to be influenced by several factors: (1) the DNA distribution and the centromeric index of the chromosomes in the various cell lines; (2) the cell cycle phase at time of micronucleus measurement due to DNA synthesis in micronuclei; (3) the presence of chromosome fragments in micronuclei; and (4) the presence of whole chromosomes in micronuclei. These factors were shown to be responsible for the previously found large radiation-induced micronuclei which could not be explained by the classic assumption only that radiation-induced micronuclei are mainly produced by single acentric fragments.

3T3 Cells

Improved time-of-flight MR angiography of the brain with magnetization transfer contrast.

The authors hypothesized that magnetization transfer contrast (MTC) could be used to improve flow contrast in time-of-flight (TOF) magnetic resonance (MR) angiography. Two- and three-dimensional flow-compensated gradient-echo images were obtained with and without MTC. MTC images were obtained by applying low-power radio-frequency (RF) radiation with a frequency offset from the bulk "free" water resonance frequency before the excitation RF pulse. The signal intensity of stationary tissue decreased as the power applied for the MTC pulse was increased. A smaller decrease occurred in venous signal intensity as measured in the superior sagittal sinus, and less change was seen in the arterial signal intensity as measured in the middle cerebral artery. Cerebrospinal fluid showed no MTC effect. The use of MTC improved small-vessel depiction on maximum-intensity projection images. The authors conclude that use of MTC can substantially enhance the quality of TOF MR angiography of the brain.

Adult

Pituitary adenomas: findings of postoperative MR imaging.

Preoperative and postoperative magnetic resonance (MR) images obtained in 25 patients with pituitary macroadenomas (1.1-5.2 cm in diameter) were evaluated to determine normal (physiologic) and abnormal findings after transsphenoidal or subfrontal surgery. With a 1.5-T unit, T1-weighted sagittal and coronal images were obtained before and after administration of gadopentetate dimeglumine. The physiologic changes after surgery included resorption of packing material and sphenoid sinus opacifications, reexpansion of the pituitary gland, and lowering of the optic chiasm. Implanted gelatin foam appeared as an endosellar, circularly enhancing mass that was seen on follow-up studies to have decreased in size. Muscle-and-fat implants appeared as areas of high signal intensity. In 14 patients, residual tumors were found in the suprasellar (n = 4), retrosellar (n = 3), parasellar (n = 8), and/or endosellar (n = 3) space. Residual tumors were differentiated from implant materials by means of location, characteristic signal intensity, and enhancing pattern, which were identical to those of the corresponding preoperative adenoma in 13 cases (93%). Preoperative studies and clinical information are helpful in the evaluation of postoperative MR imaging examinations.

Adenoma

Transaqueductal migration of a neurocysticercus cyst. Case report.

The clearly documented transaqueductal migration of a solitary intraventricular neurocysticercus cyst is described. The cyst was fortuitously demonstrated on magnetic resonance imaging during migration through the aqueduct. The radiological appearance and clinical significance of this condition are discussed.

Adult

MRI of spondylitis.

MRI of proven spondylitis was performed in 39 patients. Acute spondylitis appeared hypointense on T1-weighted and hyperintense on T2-weighted images. Following intravenous administration of Gd-DTPA, enhancement of the marrow and disc was seen. With progressive healing an increasing signal was seen on T1-weighted images. This was caused by the presence of focal fat marrow representing the first sign of therapy response. As healing progressed, the T1-signal increased due to fatty marrow, while the T2-signal decreased as well as the enhancement following Gd-DTPA administration. Therefore, MR imaging can be recommended as the method of choice for early diagnosis of spondylitis and assessment of therapy response.

Adult

Differential regulation of the expression of proteinases/antiproteinases in fibroblasts. Effects of interleukin-1 and platelet-derived growth factor.

We have previously reported that polypeptide growth factors had an anti-inflammatory effect by decreasing the cytokine-enhanced expression of factor B (FB), an activator of the alternative complement pathway, in human fibroblasts. To further characterize the role of cytokines and growth factors in the inflammatory/repair continuum, we have studied the effects of interleukin-1 (IL-1) and platelet-derived growth factor (PDGF) on the expression of metalloproteinases/antiproteinases of the extracellular matrix in cultured human fibroblasts. Co-incubation of IL-1 and PDGF synergistically increased the expression of stromelysin and interstitial collagenase to 23-fold (for both proteins) over background, while PDGF decreased the IL-1-enhanced expression of FB by 82%. PDGF, but not IL-1, alone or in combination, increased the synthesis of tissue inhibitor of metalloproteinases. RNA blot analysis indicated that the changes in protein synthesis were regulated at a pretranslational level. Cycloheximide treatment indicated that the effects of PDGF on the metalloproteinases/antiproteinases were not protein-dependent, in contrast to results obtained for FB. The effect of the three dimeric forms of PDGF (AA, AB, and BB) on the synthesis of metalloproteinases and FB was also analyzed. The effects were qualitatively similar for each of the dimeric forms; however, the BB and AB isoforms had considerably greater effects than PDGF-AA. It has been reported that the PDGF receptors found in human fibroblasts have higher binding affinity for the BB and AB isoforms of the growth factor. The results presented in this paper are in accord with the possibility that differences in the biological activity of the three isoforms of PDGF are due to differences in the number or affinity of the binding sites of the target cells, rather than to different activation pathways of the receptor. Thus, PDGF increased cytokine effects on metalloproteinases, while decreasing cytokine effects or complement activator FB. The net effect of these changes may be to decrease inflammation and enhance remodeling early in repair and to enhance matrix stability later in the repair process.

Blotting, Northern

Evolution of the major histocompatibility complex: molecular cloning of major histocompatibility complex class I from the amphibian Xenopus.

Class I major histocompatibility complex (MHC) cDNA clones have been isolated from an expression library derived from mRNA of an MHC homozygous Xenopus laevis. The nucleotide and predicted amino acid sequences show definite similarity to MHC class I molecules of higher vertebrates. The immunoglobulin-like alpha-3 domain is more similar to the immunoglobulin-like domains of mammalian class II beta chains than to those of mammalian class I molecules, and a tree based on nucleotide sequences of representative MHC genes is presented.

Amino Acid Sequence

MRI in basal ganglia diseases.

76 patients suffering from different basal ganglia diseases (28 cases with M. Parkinson, secondary parkinsonism and Parkinson diseases; 5 cases with Chorea Huntington; 5 cases with Fahr disease and 38 cases with M. Wilson) MRI featured 2 characteristical patterns: 1. abnormal deposition of minerals, 2. focal atrophies of involved organs. Thus MRI provides with informations about: 1. differential diagnosis in clinically misleading courses, 2. stage and, as a consequence, prognosis of some diseases, 3. biochemical processes of diseases in vivo.

Adolescent

A marked drop in the incidence of the null allele of the B gene of the fourth component of complement (C4B*Q0) in elderly subjects: C4B*Q0 as a probable negative selection factor for survival.

The incidence of allotypes of the genes of the fourth component (C4) and factor B of the complement system was compared in 252 persons under 45 years of age ("young" group) with 482 people between 61 and 90 years of age ("old" group). One hundred people older than 90 years of age (nonagenarians) were also investigated. A striking difference was found between the "young" and "old" groups in the incidence (16.1% and 5.4%, respectively) of a silent gene of the C4B allele (C4B*Q0). This difference was even more marked among "young" and "old" men (17.6% vs 3.4%). The incidence of the C4B*Q0 allele in women dropped to the level of the men only in the nonagenarian group. The most probable explanation for this finding is that people carrying the C4B*Q0 allele die from as yet unidentified disease(s) in their middle-age. Therefore, male (and to a lesser extent female) carriers of this allele may have a considerably shorter life expectancy than individuals without a silent gene in the C4B locus.

Adult

Potential markers of the atherosclerotic process in high-risk children.

Children whose parents had early coronary heart disease were investigated. In order to assess high-risk parameters serum total cholesterol (TC), total triglyceride (TT), high-density lipoprotein cholesterol (HDLC), low-density lipoprotein cholesterol (LDLC), lipid peroxide (LP), prostacyclin (PGI2), thromboxane (TX) levels, and the distribution of the complement 3 (C3), protein phenotypes were measured. Compared to a group of control children, the offspring of high-risk subjects had increased LDLC, LP, TC, and TX levels, a higher incidence of fast-slow heterozygotes, and decreased HDLC and PGI2 levels. The measurement of serum PGI2, TX levels and the distribution of C3 protein phenotypes may give further information about the true risk of atherosclerosis.

Adolescent

HLA-DR1 is associated with vitiligo.

In Eastern Hungary, vitiligo is found to be associated with HLA-DR1. When other autoimmune disorders are also present, DR3 is also increased.

Autoimmune Diseases

Contrast-enhanced MRI for the staging of bronchogenic carcinoma: comparison with CT and histopathologic staging--preliminary results.

Nineteen patients with potentially operable bronchial carcinoma were included in a prospective study to assess the staging capabilities of plain and contrast-enhanced magnetic resonance imaging (MRI) in comparison with computed tomography (CT) and to compare the results to post-operative histopathological staging (HS). The evaluation focused on the following T-staging criteria: (i) direct invasion of the pleura; (ii) neoplastic invasion of the mediastinum; (iii) differentiation of the primary tumour from alterations of the surrounding lung parenchyma such as inflammation or atelectasis; and (iv) intrathoracic lymph node involvement by tumour. MRI and CT produced similar results for pleural invasion (sensitivity of 0.4 and 0.75 respectively and a specificity of 0.86 and 0.93 respectively). Mediastinal invasion was overdiagnosed in four patients (no false negatives), whereas CT had only one false positive result (two false negatives). Our results showed CT to be superior to MRI for the preoperative evaluation of patients suffering from bronchogenic carcinoma.

Adult

[Sudeck's disease--MRT as a new diagnostic procedure].

In this prospective study, we determined the value of MR as an imaging technique in diagnosis and therapy with the option of simultaneous assessment of bone and soft tissue. 20 patients with clinical diagnosis of reflex sympathetic dystrophy syndrome (RSDS) and positive results in radiogram and three-phase radionuclide bone scanning were examined by MR, using T1- and T2-weighted images before and after Gadolinium-DTPA i.v. Soft tissue and bone signal intensity changes can be classified in our diagnostic-therapeutic scheme and proven by histopathological changes. The differentiation between clinical stages is possible and allows an evaluation of course and therapy. The higher costs are justified by shorter examination time without using radiation.

Adult