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Biomedical subjects

J Andersen

Publications and source records attributed to J Andersen.

At least 55 records · Page 3Linked to original sources

micF RNA in ompB mutants of Escherichia coli: different pathways regulate micF RNA levels in response to osmolarity and temperature change.

The repressor RNA, micF RNA, is regulated by temperature, osmolarity, and other stress conditions during growth of Escherichia coli. Northern (RNA) blot analyses showed that levels of micF RNA differ widely in various ompB mutant strains when cells are grown at 24 degrees C in LB broth. For example, relative to the parental strain MC4100, the ompR101 mutant strain (which contains no functional OmpR) had about a 10-fold reduction in micF RNA, whereas the envZ11 strain showed about a 5-fold increase. At 37 degrees C, however, micF RNA levels in the ompR101 and envZ11 strains and other ompB mutants differed by less than two-fold compared with the level in strain MC4100, thus indicating that a factor(s) independent of the ompB locus regulates micF RNA expression with temperature increase and that there is an additional control mechanism(s) which maintains the levels of micF RNA in these mutants close to that of the wild type during growth at high temperatures. In a plasmid strain containing the micF gene but without the upstream OmpR-binding site, steady-state levels of micF RNA increased with temperature increase but did not change with osmolarity increase. This showed that osmolal regulation but not temperature regulation of micF depends on these upstream sequences and suggested that while osmolal regulation of the micF gene depends on OmpR, thermal regulation does not.

Bacterial Outer Membrane Proteins

Identification and characterization of the small nuclear ribonucleoprotein particle D' core protein.

The addition of urea to sodium dodecyl sulfate (SDS)-polyacrylamide gels has allowed the identification and characterization of the small nuclear ribonucleoprotein particle (snRNP) D' protein and has also improved resolution of the E, F, and G snRNP core proteins. In standard SDS-polyacrylamide gels, the D' and D snRNP core proteins comigrate at approximately 16 kilodaltons. The addition of urea to the separating gel caused the D' protein to shift to a slower electrophoretic mobility that is distinct from that of the D protein. The shift to a slower electrophoretic mobility in the presence of urea suggests that the D' protein has extensive secondary structure that is not totally disrupted by SDS alone. Both N-terminal sequencing and partial peptide maps indicate that the D and D' proteins are distinct gene products, and the sequence data have identified the faster moving of the two proteins as the previously cloned D protein (L. A. Rokeach, J. A. Haselby, and S. O. Hoch, Proc. Natl. Acad. Sci. USA 85:4832-4836, 1988). In the cytoplasm, the D protein is found primarily in the small-nuclear-RNA-free 6S protein complexes, while the D' protein is found primarily in the 20S protein complexes. Like the D protein, the D' protein is an autoantigen in patients with systemic lupus erythematosus and is recognized by some of the Sm class of autoimmune antisera.

Animals

A technique for screening of achlorhydria and hypochlorhydria during upper gastrointestinal endoscopy.

Measuring of the intragastric pH during upper gastrointestinal endoscopy examination was performed perendoscopically with a monocrystalline antimony electrode, which was passed through the biopsy channel of the endoscope. The procedure was easily performed, resulting in only a few minutes' delay. If the pH found was 3.5 or above, the patients were later sent for a subcutaneous pentagastrin aspiration test. There was a close correlation between the lowest intragastric pH measured via the endoscope and the lowest pH measured in the gastric juice aspirated under basal conditions (r = 0.673, p less than 0.0001). An endoscopically assessed pH of 4.0 was the lowest level above which patients with achlorhydria or hypochlorhydria were found, according to the subsequent pentagastrin test. Fifty-five per cent of the patients with a perendoscopically assessed pH of 4.0 or above were achlorhydric.

Achlorhydria

Perioperative blood transfusion and recurrence and death after resection for cancer of the colon and rectum.

Several reports have claimed that perioperative blood transfusion promotes recurrence and death after cancer surgery. We studied the effect of transfusion in 315 patients who had radical resection for carcinoma of the colon and rectum. The disease recurred in 113 (42%) of 268 transfused patients, versus in 15 (32%) in 47 non-transfused patients (P = 0.2). Of the transfused patients 102 (38%) died of colon cancer, versus 13 patients (28%) in the non-transfused group (P = 0.2). The 5-year recurrence-free survival rate was 0.59 in the transfused patients and 0.72 in the non-transfused group (P = 0.10). When differences in confounding background variables were accounted for by Cox multiple regression analysis, the significance of transfusion was even less. The study does not support the hypothesis that perioperative blood transfusion promotes recurrence after operation for colorectal cancer.

Adult

Phase III trial of cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) versus cisplatin, etoposide, bleomycin and prednisone (CisEBP) for the treatment of advanced non-Hodgkin's lymphoma of high grade malignancy. The Danish Lymphoma Study Group.

The trial included 85 previously untreated patients (median age 61 years) with stage III or IV non-Hodgkin's lymphoma (NHL) of the subtypes centrocytic lymphoma, diffuse centroblastic lymphoma, immunocytoma, immunoblastic lymphoma, or unclassified lymphoma of high grade malignancy. The patients were randomized to 9 monthly treatment cycles of CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) or CisEBP (cisplatin, bleomycin, etoposide, prednisone). Patients who had failed to achieve even a partial response (PR) after the completion of 2 cycles were switched to the alternative regimen. Complete response (CR) on primary treatment was obtained in 70% (55-83%) of CHOP-treated patients and in 25% (13-41%) of CisEBP-treated patients (p = 0.0004). Secondary CHOP treatment produced CR in 7 (30%) of 24 patients and secondary CisEBP treatment led to CR in 2 (15%) of 14 patients. The median survival was 3.4 years in the CHOP arm and 2.6 years in the CisEBP arm (p = 0.78). Hematologic toxicity was mainly leukocytopenia and anemia in both treatment arms. Non-hematological toxicity was slight, and late toxicity was insignificant. Three treatment-related deaths were noted. We conclude that CHOP induces more remissions than CisEBP in advanced lymphomas of high grade malignancy.

Adult

In situ carcinomas of the female breast. Diagnostic and therapeutic aspects with special reference to histological growth patterns. Clinical review.

There is a disparity between the autopsy prevalence and the clinical incidence of in situ carcinoma of the breast without co-existing invasive carcinoma. The probability of developing in situ carcinoma is about 25%, while the cumulated risk of having the diagnosis established is less than 1%. In situ carcinoma in its pure form constitutes roughly 6% of all newly diagnosed breast cancers whereas in the most thorough mammographic screening series the incidence ranges from 8 to 16%. This excess in diagnosis comprises the ductal type in particular, primarily in its most aggressive forms, while the lobular type is no more common than in clinical series. Today in situ cancers occur chiefly as non-palpable lesions shown on mammography or as small changes accidentally discovered by the pathologist in a meticulous examination of an otherwise benign specimen. This survey also describes the traditional histopathological classification and presents in more detail a new classification based on histological growth patterns. The advantage of classifying in situ cancer according to its growth pattern is that it shows a good correlation with its clinical presentation. Moreover, the growth pattern can indicate the extent of excision. In addition, the method also seems to be applicable to prognosis. The treatment of in situ carcinoma has not been worked out scientifically, so treatment should be kept within the framework of prospective clinical trials. This is the only way to collect useful data about the biological behaviour of such lesions. In several countries large multicentre studies are being conducted to extend our knowledge about carcinoma in situ and to create a rational basis for treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Breast

Immunohistochemical estrogen receptor determination in paraffin-embedded tissue. Prediction of response to hormonal treatment in advanced breast cancer.

A new immunohistochemical assay using a monoclonal estrogen receptor (ER) antibody (H222, Abbott Laboratories, North Chicago) for determination of ER in formalin-fixed paraffin-embedded tissue was applied to evaluate its clinical value in a group of 145 previously untreated patients with advanced breast cancer. Suitable histologic material was accessible in 137 of these patients, of whom 70% had ER-positive tumors. The ER-positive patients had a significantly longer median overall survival than ER-negative patients (67 versus 32 months, P much less than 0.001) and this was an effect of both a prolonged disease-free interval (27 versus 17 months, P less than 0.05) and a prolonged survival after recurrence (41 versus 15 months, P much less than 0.001). Response to endocrine therapy was obtained in 49% of the patients with ER-positive tumors and in 7% with ER-negative tumors (P much less than 0.001). Relationship between response and semiquantified individual staining features could not be established. It is concluded that ER analysis in formalin-fixed paraffin-embedded tissue offers clinically useful information for allocation of patients to endocrine therapy.

Aged

Anti-B-cell monoclonal antibody-purged autologous bone marrow transplantation for B-cell non-Hodgkin's lymphoma: phenotypic reconstitution and B-cell function.

In the present report we have attempted to examine immunologic reconstitution following high-dose chemoradiotherapy and anti-B-cell monoclonal antibody (MoAb)-purged autologous bone marrow transplantation (ABMT). By cell-surface phenotypic analysis, the majority of patients had normal percentage of natural killer cells (NK), monocytes, and CD8+ T cells at one month post-ABMT. In contrast, the percentage of CD4+ T cells was reduced for at least 3 years, and the CD4:CD8 ratio reflected this imbalance. B-cell reconstitution was slightly prolonged, with normal percentage and absolute numbers of CD20+ B cells evident by 3 months. Although B cells returned by 3 months, in vitro assessment of B-cell function demonstrated impairment of proliferative responses to either anti-immunoglobulins bound to beads (anti-Ig), Epstein-Barr virus (EBV), or interleukin-2 (IL-2) for approximately 1 year and low molecular B-cell growth factor (BCGF) for approximately 2 or more years. Moreover, in vivo B-cell reconstitution demonstrated a more selective defect, with normal levels of immunoglobulin IgM returning at 6 months, IgG at 12 months, and IgA after 2 years. Despite normal numbers of B cells and relative normal levels of Ig early following ABMT, our in vitro data suggest an intrinsic defect in B-cell responsiveness. Moreover, these defects are similar to those observed following nonpurged autologous and allogeneic BMT, although the interval of immune impairment appears more prolonged.

Antibodies, Monoclonal

The function of micF RNA. micF RNA is a major factor in the thermal regulation of OmpF protein in Escherichia coli.

The role of chromosomally derived micF RNA as a repressor of outer membrane protein OmpF of Escherichia coli was examined for various growth conditions. Levels of micF RNA as determined by Northern analyses are found to increase in response to cell growth at high temperature, in high osmolarity or in the presence of ethanol. After a switch to higher growth temperature, the levels of ompF mRNA and of newly synthesized OmpF decrease with time in E. coli strain, MC4100 but these decreases are not observed in isogenic micF deletion strain, SM3001. In addition, while levels of ompF mRNA are substantially reduced in both strains in response to high osmolarity or ethanol at 24 degrees C, the reduced levels in the parental strain are still 4-5-fold lower compared with the micF deletion strain. These findings indicate that chromosomally derived micF RNA plays a major role in the thermal regulation of OmpF and represses OmpF synthesis in response to several environmental signals by decreasing the levels of ompF mRNA. Analyses of the effect of a multicopy micF plasmid on the levels of OmpF and ompF mRNA after an increase in temperature indicated that multicopies of micF RNA markedly inhibited OmpF synthesis but did not accentuate ompF mRNA decrease. These data suggest that multicopy micF inhibits OmpF synthesis primarily through translational inactivation of ompF mRNA and that a limiting factor in addition to micF RNA is necessary to destabilize ompF mRNA.

Bacterial Outer Membrane Proteins

Association of higher molecular weight ribonucleoproteins of 7 S particle preparations with multimers of transcription factor IIIA.

High molecular weight (HMW) fractions of Xenopus laevis 7 S ribonucleoprotein (RNP) particle preparations were analyzed for RNA and protein content. RNA/protein ratios, amino acid analyses and Western blots reveal that the major HMW fraction from a non-denaturing polyacrylamide gel (band b) contains two molecules of transcription factor protein IIIA (TFIIIA) to one 5 S RNA. Another HMW band appears to contain 4 molecules of TFIIIA to one 5 S RNA. Yet another RNP band (band a) contains 5 S RNA and a protein unrelated to TFIIIA. Thus, native 7 S particle preparations contain 5 S RNA bound to multimeric forms of TFIIIA as well as to an unrelated protein. The presence of additional TFIIIA molecules associated with 7 S particles may have significance in the sequestering of TFIIIA during transcriptional regulation of the 5 S gene.

Amino Acids

[Addiction to drugs and alcohol among physicians and nurses].

A retrospective investigation based on case reports was undertaken concerning abuse of alcohol and drugs among medical staff, 44 doctors and 23 nurses, who were treated in the Department of Psychiatry, Rigshospitalet during the period 1970-1982, all of whom received treatment for more than six months. By the end of 1987, a marked excessive mortality was found and this was greatest among doctors among whom 50% had died with an average age of 45.5 years. Factors which were found to be of significance for the prognosis for duration of survival in this selected material were 1) duration of the abuse of medicine, 2) presence of mixed alcohol and drug abuse and 3) previous suicidal attempts.

Adult

Testicular function in patients with testicular cancer treated with orchiectomy alone or orchiectomy plus cisplatin-based chemotherapy.

Gonadal function was evaluated in 25 patients with metastatic testicular cancer who were treated with orchiectomy plus chemotherapy with cisplatin, vinblastine, and bleomycin (PVB) and in 21 patients with clinical stage I disease who were treated only with orchiectomy and then kept under surveillance. Four years after PVB treatment, none of the patients were azoospermic; after 5 years, the total sperm counts in 46% of the patients had reached their pretreatment levels. In the group under surveillance, sperm counts below the reference level persisted or developed in 55% of the patients. Sperm production was similar in the two groups of patients 1.5 years after treatment and beyond. We conclude that spermatogenesis is not restored in all patients treated with PVB because of both preexisting germ cell defects and treatment toxicity.

Adolescent

Germ cell function and hormonal status in patients with testicular cancer.

Sperm counts, serum gonadotropins, and androgen levels were investigated in 39 seminoma patients and 58 patients with a nonseminomatous germ cell tumor of the testis after unilateral orchiectomy. In 58% of the patients, the total sperm count was below the lower reference value (80 million). A multiregression analysis demonstrated a correlation between a decreased total sperm count and the following three explanatory variables: (1) an elevated serum alpha-fetoprotein (AFP), (2) a history of chryptorchidism, or (3) a seminomatous tumor. In 42% of the patients, the sperm concentration and the sperm motility met criteria considered sufficient for cryopreservation. Serum follicle-stimulating hormone (FSH) was elevated in 33% of the patients. Androgens (serum testosterone [T] or urine 17-oxy-steroids [17-OS]) were subnormal in 5% of the patients, whereas serum luteinizing hormone (LH) was elevated in 14% of the patients without human chorionic gonadotropin beta-subunit (beta-HCG) in serum.

Adult

[Tension pneumoperitoneum].

A case of tension pneumoperitoneum is presented. The importance of immediate intervention is emphasized.

Female

Predictive factors for long-term survival in patients with advanced ovarian cancer.

A total of 107 patients with carcinoma of the ovary were entered in a study combining extensive primary surgery and intensive chemotherapy. Because of evidence supporting the effectiveness of both single agent platinum (P) and the combination of cyclophosphamide and doxorubicin (CA), patients were treated with alternating cycles of CA and CP. Primary surgery to remove the bulk of tumor to less than 2 cm was possible in 45% of the 85 eligible patients, and an additional 17% had similar surgery after two to four cycles of chemotherapy. Fifteen percent of patients progressed on chemotherapy. Of the 68 who were clinically and radiologically without disease at the completion of chemotherapy, 91% had second-look surgery. Forty-eight percent of these women had residual disease. All patients but one are at risk for greater than 60 months, with a median follow-up of 86 months. Overall 5-year survival is 26%, with a median survival of 33 months. Twenty patients survived over 5 years with 11 continuing to be free of disease (13% of all eligible patients). Patients with modified Broder's grade I,II tumors have not yet reached a median survival. Grade, stage, and primary mass size were the only variables with independent prognostic value in a Cox multivariate analysis.

Adult