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Biomedical subjects

D A Hansen

Publications and source records attributed to D A Hansen.

At least 19 recordsLinked to original sources

Assessment of proliferative activity in breast cancer: MIB-1 immunohistochemistry versus mitotic figure count.

The proliferative activity is one of the most important single prognostic parameters in breast cancer diagnosis and the time-honored measure of proliferative activity, the mitotic figure count, is an integral component of most combined prognostic scores. The detection of the cell cycle-specific antigens Ki-67, and the development of anti-Ki-67 antibodies, including the paraffin-reactive antibody MIB-1, have established immunohistochemical detection of cell cycle-specific antigens as a measure of proliferative activity in breast cancer diagnosis. The current study was performed to correlate mitotic figure counts with the proliferative activity as assessed by MIB-1 immunohistochemistry, taking into consideration the interobserver reliability of 5 pathologists in estimating mitotic figure counts. In 32 consecutive invasive ductal breast carcinomas, mitotic figure counts were performed independently by 5 pathologists. Mitotic activity was expressed as number of mitotic figures per 10 high-power fields and in a 3-tier score according to the Scarff Bloom Richardson system. Immunohistochemistry was performed using MIB-1 antibody, heat-induced epitope retrieval, and the standard avidin-biotin-immunoperoxidase method. MIB-1 immunohistochemistry was assessed in 3 representative 20x fields by semiquantitative estimation (% of tumor cells positive) and by image analysis (number of MIB-1-positive cells/mm2). We found a high degree of interobserver correlation among 4 experienced pathologists, in both mitotic figures per 10 high-power fields and the 3-tier scoring system. We observed significant, albeit weak, correlations between semiquantitative and quantitative MIB-1 immunohistochemistry and the number of mitotic figures per 10 high-power fields (r between .36 and .53), but this significance was lost in 3 of the 5 observers when mitotic activity was expressed in the 3-tier scoring system. This study confirms mitotic figure counting in the hands of experienced pathologists as a valid, reproducible means of assessing proliferative activity in routine breast cancer diagnosis. The statistically significant, albeit only weak, correlation with MIB-1 immunohistochemistry is in agreement with results obtained by others and suggests that MIB-1 immunohistochemistry cannot be translated by a simple conversion factor into combined prognostic scores to replace the time-honored mitotic figure counts.

Antigens, Nuclear↗

Keratinocyte apoptosis following bone marrow transplantation: evidence for CTL-dependent and -independent pathways.

Acute graft-versus-host disease (GVHD) is a complication of bone marrow transplantation (BMT). The histopathologic features used to diagnose GVHD are nonspecific, and may be secondary to chemotherapy or irradiation given before BMT. The presence of apoptotic keratinocytes or activated CTL may distinguish GVHD from conditioning effects. This study investigated the relationship in BMT recipients between keratinocyte apoptosis and the effects of conditioning regimens or immune-mediated GVHD. Inflammatory cells, apoptotic keratinocytes, and CTL expressing TIA-1 (a molecule associated with the lytic granules of CTL) were quantitated in allogeneic and autologous recipients. Allogeneic recipients could exhibit keratinocyte apoptosis secondary to a combination of conditioning effects and immune-mediated GVHD. In contrast, autologous recipients should show conditioning effects only. 'Capped' TIA-1-positive lymphocytes and apoptotic keratinocytes were much more frequent in the allogeneic group than the autologous group (16.1% of total TIA-1 positive lymphocytes vs 4.5%, P=0.02; and 37.6/mm2 vs 3.9/mm2, P = 0.005, respectively), although there was some overlap in their frequency. Among individual recipients of allogeneic BMT, the number of epidermal lymphocytes or macrophages correlated with the number of apoptotic keratinocytes. A similar, but weaker, correlation was seen between the number of 'capped' TIA-1-positive lymphocytes and apoptotic keratinocytes. No such relationship was seen in autologous recipients. In allogeneic recipients, TIA-1 expressing CTL were seen in intimate contact with apoptotic keratinocytes, some of which also had detectable cytoplasmic TIA-1. No CTL/keratinocyte interactions were identified in autologous recipients. Our results suggest that apoptotic keratinocytes arise in the skin of BMT patients due to both GVHD and conditioning effects, and that the keratinocyte damage in GVHD is mediated by both CTL-dependent and -independent mechanisms. Increased numbers of apoptotic keratinocytes, in the presence of increased epidermal lymphocytes or 'capped' TIA-l-expressing lymphocytes, support a diagnosis of GVHD, but must be interpreted in the context of clinical information and other histopathologic findings.

Apoptosis↗

Identification of monoclonal immunoglobulins and quantitative immunoglobulin abnormalities in hairy cell leukemia and chronic lymphocytic leukemia.

Serum and urine samples from 161 cases of hairy cell leukemia (HCL) and 50 cases of chronic lymphocytic leukemia (CLL) were analyzed for monoclonal immunoglobulin (MIg) by using a combination of high-resolution protein electrophoresis, immunoelectrophoresis, and immunofixation. Quantitative immunoglobulin analysis also was performed on all serum samples. Monoclonal immunoglobulin, usually of low intensity, was identified in serum or urine in 26 (16.1%) cases of HCL compared with 27 (54%) cases of CLL. Forty-eight (29.8%) cases of HCL had an increase in one or more immunoglobulins; increases in IgG were the most frequent. In CLL, 48 (96.0%) cases had a decrease in one or more immunoglobulins, with decreases in IgG, IgA, and IgM in 76%, 68%, and 56% of the cases, respectively. The correlation between serum or urine monoclonal immunoglobulin light chain and the surface membrane light chain was 88% in CLL compared with 47.4% in HCL. These findings confirm previous observations of frequent polyclonal hyper-gamma-globulinemia in HCL, hypo-gamma-globulinemia in CLL, and weak monoclonal immunoglobulins in both disorders. The contrasting immunoglobulin abnormalities in HCL and CLL indicate distinctive biologic differences in these chronic B-cell leukemias.

Adult↗

Indocyanine green (ICG) staining and demarcation of tumor margins in a rat glioma model.

The ability of indocyanine green (ICG) to stain and demarcate brain tumor margins was investigated using an intracerebral rat glioma model. Indocyanine green was injected intravenously into tumor-bearing rats and was found to stain the tumor intensely at 60 to 120 mg/kg for at least 1 hour after injection. Furthermore, gross tissue staining was found to coincide with the actual histologic tumor margins within 1 mm. After resection of stained tumor tissue, minimal residual tumor cells at the margins of the resection cavity were identified. This investigation established the capacity of indocyanine green to grossly delineate a rat brain tumor and its margins from adjacent normal parenchyma.

Animals↗

Noise exposure in the rural setting.

Noise levels of 155 tractors on 36 farms were studied. The range of noise levels at the driver's ear level with radios off and windows closed (if so equipped) was from 78 to 103 dB. Seventy-five percent of tractors without cabs had noise levels in excess of 90 dB, compared to only 18% of tractors with cabs. The use of a radio adds an average of 3.1 dB of noise. When some cab windows are open and the radio is on, an average of 4.2 dB is added to the cab noise. From the results of this study, the authors recommend hearing protection when time on a tractor with a cab approaches 3 to 4 hours and when time on a tractor without a cab approaches 1.5 to 2 hours. Limited use of the radio is also recommended.

Acoustics↗

[Hospital employees' knowledge about HIV disease. A study from 2 provincial hospitals].

The knowledge of and attitudes to HIV infection were investigated by means of questionnaires during the period 1.10.1988 to 30.4.1989 in two small Danish Hospitals. Two hundred and thirty two nurses, 147 nursing aids, 44 doctors, 25 laboratory workers and 22 midwives took part in the investigation. The overall response was 99% of the staff contacted. The questionnaires were anonymous and were completed immediately and without use of any sources of information. Poor knowledge was revealed concerning symptoms, sources of infection, precautions to avoid infection, high-risk groups and patients duty to provide information. In fact, none of the groups exceeded 66% correct answers on these subjects. A total of 70% of the whole group had been in contact with patients, whom they suspected to be HIV-positive. Every third individual had felt insecure regarding HIV at work. Incidents at work had caused 18 employees to be tested for HIV. Only about half had been instructed about HIV. A total of 73% expressed needs for further instruction about the disease. The investigation shows difference between the staff opinion of possible claims on the patients about tests and to the policy of the Danish Department of Health concerning voluntary testing.

Denmark↗

Hearing loss among high school farm students.

To study the prevalence of hearing loss among teen-aged farm children in central Wisconsin, audiometric threshold testing of 872 vocational agriculture students was carried out over a three-year period. The results indicate an increased prevalence of hearing loss among students actively involved in farm work, as compared to their peers not involved in farm work. Findings also suggest that use of hearing protection may reduce the risk of hearing loss among students who work on the farm, although few students report the use of such devices. These data also suggest that the hearing loss often observed in adult farmers may begin in childhood.

Adolescent↗

Developmental regulation of globin and nonglobin messenger RNAs in avian erythroid cells.

During embryonic development in the chicken two morphologically distinct erythroid cell populations sequentially appear. Coincidentally with the change in cell populations that begins on the sixth day of embryonic life, the hemoglobins of the early embryo are gradually replaced by a new set of hemoglobins, which are almost identical to those of the adult chicken. We have used recombinant DNAs to investigate the molecular mechanisms underlying these developmental changes. With respect to the eight nonglobin species of messenger RNA that we have studied, seven are present at approximately equal concentrations in erythroid cells from 5-day embryos and from anemic adults. This suggests that the replacement of erythroid cell populations is not accompanied by a general reorganization of gene expression. With respect to globin gene expression, however, we find that all but one of the globin genes studied (alpha D-globin) undergo dramatic developmental regulation. We have also shown that the expression of the gene for the embryo specific alpha-like globin, pi'-globin, is principally regulated at the level of transcription.

Animals↗

Limitation of myocardial infarct size in patients less than 66 years treated with alprenolol.

Two hundred and eighty-two patients less than 66 years of age admitted with suspected or definite myocardial infarction were allocated in a random fashion to treatment with alprenolol or placebo. Treatment was started immediately upon admission with 5-10 mg alprenolol or placebo intravenously, followed by 200 mg alprenolol or placebo orally twice a day for one year. In 178 patients a definite myocardial infarction was diagnosed. Myocardial infarct size could be estimated from serial determinations of serum total creatine kinase in 42 patients treated with alprenolol and 43 patients receiving placebos. Median infarct size was 20.6 CK g Eq/m2 body surface in the alprenolol group, the corresponding figure in the placebo group being 34.4 CK g Eq/m2 body surface. Median rate of release of creatine kinase from the ischaemic myocardium was 27.7 U/1 per hour and 48.0 U/1 per hour after alprenolol and placebo, respectively. Alprenolol limited infarct size significantly provided the treatment was started within 12 hours of the onset of symptoms.

Aged↗