Expression of retinoblastoma protein in human growth hormone-secreting pituitary adenomas

The retinoblastoma gene (RB1) is a tumor-suppressor gene in chromosomal region 13q14.2. Its role in the pathogenesis of pituitary tumors has not been fully clarified. Some studies have shown that losses in this chromosomal region are related to aggressive tumor behavior, although the retinoblastoma protein (pRB) is still expressed. Conversely, lack of expression of pRB was observed in one fourth of GH-secreting pituitary adenomas (GH-tumors). In order to further study the expression of pRB in GH-tumors, we evaluated this protein in 49 tumors from patients with acromegaly (20 noninvasive, 25 invasive, and 4 with no information) and 8 normal pituitaries using immunohistochemistry (IHC). Nuclear staining for pRB ranged from 0 to 90% (median 40%) in the tumors and from 40 to 80% (median 58%) in normal pituitaries. In 10 tumors (20% of total) the adenomatous cells were negative (5 cases) or had very low labeling (5 cases) for pRB. Sixty three percent (31/49) of the tumors showed staining in 10–80% of the cells and in 16% (8/49) of the cases >80% of the adenomatous cells were positive for pRB. The expression of pRB was not different in invasive and noninvasive tumors. In conclusion, pRB is underexpressed in a subgroup of GH-tumors, and this may represent an early event in the pathogenesis of this tumor subtype.     

Retinoblastoma and p53 gene product expression in breast carcinoma: Immunohistochemical analysis and clinicopathologic correlation

We examined 100 breast cancers for retinoblastoma (Rb) and p53 protein expression by immunohistochemistry using the PMG3.245 and PAb 1801 antibodies. We assessed percentages of reactive cells and their intensity, as well as staining patterns. The results were correlated with neu protein reactivity and a panel of variables, including age, tumor size and type, nuclear grade, estrogen receptor/progesterone receptor content, and lymph node status. Retinoblastoma protein negativity, either partial or complete, was noted in 47% of cases. Surprisingly, a relatively stronger Rb reaction was seen in some high nuclear grade tumors. p53 positivity was found in 23% of cases and was a significant predictor of Rb loss. p53 also was correlated with poorly differentiated (nuclear grade III) neoplasms and neu expression but not with negative ER status. Tissue distribution profiles for Rb-negative and p53-positive cells were variable in this series, with both uniform and heterogeneous patterns observed. This suggests that Rb and p53 alterations may represent early or late events in transformation. Our findings further implicate Rb and p53 derangements in mammary oncogenesis.     

Psychological reactions in patients with early rheumatoid arthritis

We report the interaction of RA and psychological factors over 2 years in a group of 89 patients with newly established disease. Short-time outcome regarding physical features was fairly good. Disease activity decreased, and disability evaluated by HAQ remained at a low level. Psychological distress as measured by the depression and anxiety subscales of SCL 90 (Symptom Check List) was not very pronounced and not related to disease state factors. A slight decrease of anxiety was recorded after 2 years. A new adjustment test was applied. It contained 13 items focused mainly on negative illness effects such as loss of independence, feelings of guilt, and change of social and leisure time activities. Three factors (regret of lost life values, dysphoric mood, and acceptance) explained 48% of the variance of the 13 items. The validity of the test was acceptable. The patients' degree of adjustment changed slowly or not at all during the 2 years.     

Effect of short physical exercise on the levels of zinc and carbonic anhydrase isoenzyme activities in human erythrocytes

Summary Studies of the influences of physical exercise of short duration (bicycle ergometer, 200 W for 30 min) on the activities of carbonic anhydrase isoenzymes (CA-B and CA-C types) and zinc concentration in erythrocytes were made on 5 untrained healthy male volunteers. The subjects were rested for 30 min after the exercise. There were significant decreases in the levels of zinc, CA-B, total carbonic anhydrase activity and CA-B-dependent activity immediately after exercise, but after 30 min of rest they all returned to their pre-exercise levels. No significant change in CA-C level or CA-C-dependent activity was found after exercise. Immediately after exercise, total carbonic anhydrase activity and CA-B-dependent activity following the addition of Zn²⁺ showed significant increases, compared with their respective activities without Zn²⁺ addition. However, no such effects were observed just before exercise or after rest; the addition of Zn²⁺ had no effect on CA-C-dependent activity at any time. A significant correlation was found between the changes in concentration of zinc and CA-B-dependent activity after exercise (r=0.711). The findings of the present study suggest that active CA-B enzymes are converted in part to inactive enzymes during acute physical exercise, possibly by decreased zinc binding. Moreover, the change in CA-B-dependent activity correlated well with the changes in pH and HCO₃ concentrations in venous blood (r=0.853 and r=0.718, respectively). One may speculate that an adaptive decrease in CA-B-dependent activity in erythrocytes occurs with increased acidification in blood during heavy physical exercise of short duration.The present study was presented to the Fifth International Symposium on the Biochemistry of Exercise, Boston, June 1–5, 1982     

The rheumatic patient''s early needs and expectations

During the last few years, studies have revealed that the need for psychosocial support and concrete social services are great in the early stages of the treatment of rheumatic diseases. The ability to keep a job, to do household chores, to participate in leisure activities and to maintain social relations is clearly impaired. Anxiety and depression are not unusual and often associated with weak support from relatives, loneliness and disturbed family relations. Nevertheless, the patients report resilience and determination to cope with the impacts of illness. Crisis intervention, vocational guidance and counselling about problems concerning the disease should be available and offered to the patients. As the patients seem to be unaccustomed to talking about their psychosocial problems, an empathetic and information-seeking attitude on the part of the health care staff is essential.     

Time-resolved particle image velocimetry and laser doppler anemometry study of the turbulent flow field of bileaflet mechanical mitral prostheses

Dynamic particle image velocimetry (PIV) was applied to the study of the flow field associated with prosthetic heart valves. The results were compared with those of laser Doppler anemometry (LDA). Anatomically and antianatomically oriented Jyros (JR) and St. Jude Medical (SJM) valves were compared in the mitral position to study the effects of valve design on the downstream flow field. The experimental program used a dynamic PIV system utilizing high-speed, high-resolution video to map the true time-resolved velocity field inside the simulated ventricle. This system was complemented by a study using the more traditional LDA system for comparison. Based on the experimental data, the following general conclusions can be made. High-resolution dynamic PIV can capture true chronological changes in the velocity and turbulence fields. It also produces very detailed velocity and turbulence information comparable to the LDA results. In the vertical measuring plane that passes both the center of the aortic and mitral valves (A-A section), the two valves (the SJM and the JR) show distinct circulatory flow patterns when the valve is installed in the antianatomical orientation. Small differences in valve design can generate noticeable differences, particularly during the accelerating flow phase. The SJM valve maintains a relatively high velocity through the central orifice; the curved leaflets of the JR valve generate higher velocities with a divergent flow during the accelerating and peak flow phases. In the velocity field directly below the mitral valve and normal to the previous measuring plane (B-B section), where characteristic differences in valve design will be visible, symmetrical twin circulations were observed because of the divergent nature of the flow generated by the two inclined half-disks installed in the antianatomical orientation. The SJM valve, with a central downward flow near the valve, is contrasted with the JR valve, which has a peripheral downward circulation with higher, turbulent stresses.     

Interaction between the immune and central nervous systems

Much of the understanding of tolerance has focused on the requirements for antigen-specific lymphocyte activation and function. However, there is increasing evidence for anatomic regulation of effector access to self antigens. Recently, a number of studies have provided evidence for tissue-specific “addressins” in chemokine/chemokine receptor pairs. The central nervous system (CNS) provides special anatomic barriers to the movement of cells from the vascular compartment to the parenchyma. Herein I raise the possibility that antigen, perhaps through specialized antigen-presenting cells, may play a role in regulating access of activated lymphocytes into the CNS parenchyma. The results suggest that a reexamination of the widely held dogma that all activated lymphocytes have access to the CNS parenchyma is nessary to understand the relationship between the immune and central nervous systems.     

The effect of immunotherapy on eosinophil accumulation and production of eosinophil chemotactic activity in the lung of subjects with asthma during natural pollen exposure

Two groups of birch pollen--allergic patients with seasonal rhinoconjunctivitis and asthma were followed during two consecutive birch-pollen seasons, one group, N = 10, during a season with high pollen load, and one group, N = 15, during a season of low pollen load. Half the patients were treated with immunotherapy (IT) for 3 and 4 years, respectively. The other half of the patients served as control group (non-IT). Bronchoalveolar lavage (BAL) was performed once before each season and once during the pollen season. Eosinophil (EOS) numbers in BAL were increased (p less than 0.01) during the season with high pollen load but not in the season with a low pollen load, and this increment was absent in the IT-treated group. Also, the EOS cationic protein levels were raised in the non-IT-treated group during the season with a high pollen load. The levels of EOS and neutrophil chemotactic activity were raised in BAL in both seasons in the non-IT-treated group compared with the IT-treated group (p less than 0.02, p less than 0.003, p less than 0.04, and p less than 0.005 in high- and low-load pollen season, respectively). Serum and BAL eosinophil chemotactic activity (ECA) were positively correlated (p less than 0.001). We conclude that there is an influx of active EOSs into the lung of pollen-allergic patients with asthma during a pollen season, which may be abrogated by IT. Furthermore, the generation of ECA appears to be an extremely sensitive marker of antigenic exposure, and the potent inhibition of the generation of ECA by IT may provide a clue as to the mechanism of this treatment.