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Biomedical subjects

J Sitzmann

Publications and source records attributed to J Sitzmann.

9 recordsLinked to original sources

Increased hepatic oxidative DNA damage in patients with hepatocellular carcinoma.

Since oxidative DNA damage plays a role in experimental carcinogen-induced cancers, the purpose of the present study was to determine if hepatic oxidative DNA damage was increased in patients with HCC compared to patients with benign hepatic tumors or hepatic metastases (non-HCC) or to patients with end-stage alcoholic liver disease undergoing liver transplantation. Oxidative DNA damage was assessed by 8-hydroxy-2'-deoxyguanosine (8-OH-dG). Results showed that peritumoral 8-OH-dG was markedly increased in HCC (N= 51) (180 +/- 74 vs 32 +/- 58-OH-dG/10(6)dG for tumor, P < 0.005) in contrast to patients with non-HCC (N = 17), in whom the peritumoral 8-OH-dG did not differ from that in tumor (39 +/- 7 vs. 31 +/- 108-OH-dG/10(6)dG). Oxidative DNA damage can be both mutagenic and carcinogenic; our data suggested it will be important in future studies to determine the chronology of this type of liver injury relative to hepatocarcinogenesis.

8-Hydroxy-2'-Deoxyguanosine↗

Excretion of low molecular weight heparin in human milk.

AIMS: The excretion of low molecular weight heparin (LMWH) in breast milk was investigated in 15 lactating mothers after Caesarean section. METHODS: Blood and milk samples were collected before and 3-4 h after once daily routine subcutaneous injection of 2500 IU dalteparin. Anti-Xa activity was measured by an assay utilizing prolonged clotting times in plasma or breast milk as an index of LMWH activity. RESULTS: Plasma anti-Xa activities ranged from 0.074 to 0.308 IU ml(-1) of plasma. Anti-Xa activities in breast milk ranged from < 0.005-0.037 IU ml(-1) of milk. This is equivalent to a milk/plasma ratio of < 0.025-0.224. CONCLUSIONS: Therefore, it appears highly unlikely that puerperal thromboprophylaxis with LMWH has any clinically relevant effect on the nursing infant.

Anticoagulants↗

Reconstruction of double hepatic arterial and portal venous branches for right-lobe living donor liver transplantation.

Double hepatic arterial and portal venous branches are common anatomic variations of the isolated right hepatic lobe. Reconstruction of these vessels during transplantation can be challenging because of their small caliber, close proximity to other hilar structures, and abnormal alignment with the native vasculature. Practical techniques for the creation of these anastomoses would simplify the recipient surgery and might minimize the incidence of vascular complications. Alternative methods for management of these structures are summarized. The recipient's proper hepatic artery and its bifurcation are resected for use as an arterial Y-type graft. The donor arteries are individually anastomosed at the bifurcation of the recipient's hepatic artery at the back table. The free end of the Y graft is then replaced at the origin of the gastroduodenal artery using standard branch-patch technique. Reconstruction of a second donor portal branch is similarly facilitated by ex situ placement of a Y-type vascular conduit derived from the recipient's portal vein. Surgical management of these vessels and reconstruction of other hilar structures are noticeably less cumbersome. There have been no short-term vascular complications. The use of autologous vascular conduits with ex situ reconstruction facilitates management of double donor arterial and portal venous branches. The incidence of complications attributable to these methods is expected to be low.

Angiography↗

Distribution and potential biologic function of the thrombin receptor PAR-1 on human keratinocytes.

Thrombin has recently been shown not only to exert procoagulant activities, but also to induce mitogenic responses of different cell types involved in wound healing via binding to and cleavage of the thrombin receptor. In order to further explore these aspects of thrombin function, human keratinocytes (HaCaT cell line) were examined for their potential mitogenic responsiveness to thrombin and for the dependency of this process on the expression of the high-affinity thrombin receptor. Quiescent keratinocytes were stimulated in the mitogenic assay with alpha-thrombin and the thrombin receptor activating peptides TRAP42-55 (SFLLRNPNDKYEPY) and TRAP42-46 (SFLLR). A strong induction of cell proliferation was noted with alpha-thrombin, TRAP42-55 and TRAP42-46, but not with the "scrambled" peptide (FSLLR). These findings confirm that keratinocytes express the thrombin receptor and that the sequence of the first two amino acids of the generated neo-N-terminus are important for the activation of the receptor. Using cDNA fragments of the 5' coding sequence of the receptor, Northern blot analysis confirmed that HaCaT keratinocytes express the thrombin receptor. Expression of the receptor was also detected on normal human keratinocytes by immunohistochemistry and in situ hybridization. These data demonstrate the expression and biologic function of the human thrombin receptor on human keratinocytes, suggesting that thrombin, among other mediators, plays an important part in the orchestration of epidermal growth and repair processes.

Blotting, Northern↗

Expression of B-Myb during mouse embryogenesis.

B-myb is a member of the myb family of nuclear sequence-specific DNA-binding proteins which has been highly conserved among vertebrates. B-myb has been implicated in the control of cell proliferation, particularly at the G1/S transition of the cell cycle. So far, most of the work on B-myb has been performed in immortalized cell lines. Since these cells might show aberrant behavior of genes involved in proliferation control we have begun to investigate the role of B-myb in normal cells. As a first step, we have studied the expression of B-myb during mouse development. Here, we show the B-myb is expressed at similar levels during all stages of embryogenesis. In situ hybridization reveals a tight linkage between B-myb expression and proliferative activity (as assessed by the expression of the S-phase specific histone H4 gene) in most tissues and throughout embryonic development. However, B-myb and histone H4 expression are uncoupled during spermatogenesis in the adult mouse. Histone H4 is expressed at high levels in the early spermatogenic progenitor cells but not in successive stages of sperm cell development. By contrast, the highest levels of B-myb expression are found during the intermediate stages of spermatogenesis. Furthermore, we have found that B-myb mRNA isolated from the testis differs in size from that of other tissues. The data presented here strongly support the notion that B-myb plays a general role during proliferation of most cells. Furthermore, our results raise the possibility that the function of B-myb in cells undergoing meiosis may be different from its role in cells dividing mitotically.

Animals↗

Differential expression of CRABP II, psoriasin and cytokeratin 1 mRNA in human skin diseases.

In order to confirm and further explore the significance of the overexpression of the CRABP II (cellular retinoic acid binding protein type II) and psoriasin genes in psoriatic versus normal skin, we examined the mRNA expression levels of these two genes by in situ hybridization in skin samples from psoriatic plaques and in one case from the border between a psoriatic plaque and uninvolved skin. Both genes were markedly upregulated in lesional skin, with a shift from low to high expression in the transitional zone of the plaque. Expression of the cytokeratin 1 (K1) gene was, in contrast, high in normal skin and decreased in the transition from uninvolved skin to psoriatic plaque, Examination of mRNA levels of CRABP II and psoriasin in other hyperproliferative and inflammatory skin diseases showed high expression of psoriasin, and in some cases also of CRABP II, in atopic dermatitis, mycosis fungoides, Darier's disease and inflammatory lichen sclerosus et atrophicus. In atrophic lesions of lichen sclerosus et atrophicus that lacked an inflammatory infiltrate, these changes were only weakly expressed. These findings demonstrate that altered epidermal gene expression of K1, psoriasin and CRABP II is not disease-specific and may reflect instead an altered state of epidermal differentiation and/or may be linked to the inflammation and cellular infiltration common to all the conditions studied.

Biopsy↗

Expression of mouse c-myb during embryonic development.

Three members of the myb gene family, designated as A-myb, B-myb, and c-myb, have been described in many vertebrates. A large body of evidence indicates that the c-myb gene is essential for the development of most hematopoietic lineages. By contrast, the functions of A-myb and B-myb are less well understood. To further explore the relationship between the different myb family members we have compared the expression of A-myb and c-myb during mouse embryogenesis by Northern blotting and by in situ hybridization. In accordance with the important role of c-myb in the hematopoietic system, we detect high levels of c-myb expression in hematopoietic organs such as the fetal liver and the thymus. Surprisingly, we find that high levels of c-myb expression are not restricted to hematopoietic cells. We show that c-myb is strongly expressed in the neural retina and in epithelia of the respiratory tract. The side-by side analysis of c-myb and A-myb expression clearly shows that both genes are expressed in different, but overlapping sets of tissues. Our results suggest that the function of c-myb may not be restricted to hematopoietic cells.

Animals↗

Synchronous mature teratomas of the ovary and liver: a case presenting 11 years following chemotherapy for immature teratoma.

Immature teratoma is a rare ovarian germ cell tumor with an aggressive clinical behavior. Treatment involves surgical resection, usually followed by chemotherapy. Since the introduction of postoperative chemotherapy several cases of "transformation" of this malignant tumor into mature teratoma (retroconversion) have been described. Usually retroconversion presents during the first year of diagnosis. We report a case of synchronous mature teratomas of the ovary and liver presenting 11 years following chemotherapy for stage III immature ovarian teratoma. The CT scan appearance, incidence, and biological significance of this phenomena are discussed.

Adult↗

Physical and genetic map of the Methanococcus voltae chromosome.

A physical map of the Methanococcus voltae chromosome was constructed on the basis of restriction mapping and cross-hybridization experiments, employing total and partial digests obtained with rarely cutting restriction enzymes. On the basis of the sum of the fragment sizes of digests with seven enzymes the chromosome length was calculated to be approximately 1900 kb. The derived map is circular. Hybridization of gene probes to mapped restriction fragments has led to a genetic map of genes for structural RNAs as well as proteins, including enzymes involved in the methanogenic pathway.

Archaea↗