Apoptosis and expression of apoptotic regulators in the human testis following short- and long-term anti-androgen treatment

Apoptosis and its augmentation by androgen withdrawal is an important event in the testis. In other tissues apoptosis is regulated by genes belonging to the bcl-2 family. However, little is known about these pathways in the human testes. Human testes were obtained from patients with prostate cancer, undergoing orchidectomy for permanent androgen ablative treatment. The patients were either untreated or had previously received short- or long-term anti-androgen therapy by cyproterone acetate or GnRH agonist (goserelin). In comparison with untreated patients, testicular testosterone concentrations were reduced by 83% in patients treated with cyproterone acetate and by 99% in patients treated with goserelin. Apoptotic cells were identified in tissue sections by in-situ end labelling of fragmented DNA. The expression of Bcl-2, Bcl-xl, Bax, p53 and poly(ADP) ribose polymerase (PARP) was demonstrated in tissue extracts by Western blotting. Apoptotic germ cells were present in the spermatogenic epithelium of untreated patients and patients who received short-term anti-androgen treatment. There were few or no apoptotic cells in the seminiferous tubules following long-term anti-androgen treatment. Following short- term treatment, the concentrations of the apoptosis-related proteins examined did not change. However, in the long-term treated testes, Bcl- xl and PARP expression declined, Bax and p53 protein concentrations were unchanged, and Bcl-2 was up-regulated. In conclusion, apoptosis occurs in spermatogenic cells of the human testis and may contribute to the regulation of germ cell populations. The apoptosis-related gene products which have been described in other tissues are present in the human testis and are modulated by androgenic stimuli.      

Monoclonal antibody 12-8 recognizes a 115-kd molecule present on both unipotent and multipotent hematopoietic colony-forming cells and their precursors

A monoclonal antibody, 12-8, prepared against KG-1a cells, recognizes an approximately 115-kd cell surface antigen and reacts with 3% to 4% of bone marrow cells, including most of the blast cells. The antigen is not expressed on peripheral blood cells. Marrow cells expressing 12-8 collected by fluorescence-activated cell sorting contained nearly all of the unipotent (CFU-GM, BFU-E) and multipotent (CFU-MIX) colony- forming cells. The isolated 12-8 positive marrow population also contained precursors of these colony-forming cells. In a two-stage long- term marrow culture system employing irradiated allogeneic marrow adherent cells, 12-8 positive cells produced both unipotent and multipotent colony-forming cells for ten weeks. Moreover, the output of colony forming cells substantially exceeded the input. Antibody 12-8 appears useful for analysis and possibly enrichment of hematopoietic progenitor cells that include colony-forming cell precursors.     

The L4F3 antigen is expressed by unipotent and multipotent colony- forming cells but not by their precursors

Antibody L4F3 is a murine monoclonal antibody that recognizes an antigen expressed on in vitro colony-forming cells, including virtually all CFU-GM, CFU-Meg, BFU-E, and CFU-Mix. In the present study we examined whether cells that do not express the L4F3 antigen include precursors of hematopoietic colony-forming cells. Colony-forming cells were depleted from marrow by treatment with L4F3 and complement. The remaining cells generated CFU-GM, BFU-E, and CFU-Mix when cultured in the presence of irradiated adherent cell layers from long-term marrow cultures. Marrow cells not expressing the L4F3 antigen, which were separated by cell-sorting techniques, were depleted of colony-forming cells but nevertheless generated CFU-GM when cultured over irradiated adherent cell layers. These data suggest that there are marrow precursors that do not express the L4F3 antigen and that give rise to colony-forming cells of multiple types. Negative selection techniques should allow the enrichment of these precursors of colony-forming cells, thereby enabling direct studies of these immature stem cells.     

Cerebellar theta burst stimulation does not improve freezing of gait in patients with Parkinson’s disease

Freezing of gait (FOG) in Parkinson’s disease (PD) likely results from dysfunction within a complex neural gait circuitry involving multiple brain regions. Herein, cerebellar activity is increased in patients compared to healthy subjects. This cerebellar involvement has been proposed to be compensatory. We hypothesized that patients with FOG would have a reduced ability to recruit the cerebellum to compensate for dysfunction in other brain areas. In this study cerebellar activity was modified unilaterally by either excitatory or inhibitory theta burst stimulation (TBS), applied during two separate sessions. The ipsilateral cerebellar hemisphere, corresponding to the body side most affected by PD, was stimulated. Seventeen patients with PD showing ‘off’ state FOG participated. The presence of FOG was verified objectively upon inclusion. We monitored gait and bimanual rhythmic upper limb movements before and directly after TBS. Gait was evaluated with a FOG-provoking protocol, including rapid 360° turns and a 10-m walking test with small fast steps. Upper limb movement performance was evaluated with a repetitive finger flexion–extension task. TBS did not affect the amount of freezing during walking or finger tapping. However, TBS did increase gait speed when walking with small steps, and decreased gait speed when walking as fast as possible with a normal step size. The changes in gait speed were not accompanied by changes in corticospinal excitability of M1. Unilateral cerebellar TBS did not improve FOG. However, changes in gait speed were found which suggests a role of the cerebellum in PD.     

The growth of uterine myomas in untreated women: influence factors and ultrasound monitoring

Purpose

Until now there are no systematic studies about the long-term course of myoma growth. Therefore, the aims of the present study were: (1) ultrasound monitoring of the natural course of growth of uterine leiomyomas; (2) assessment of whether the growth of myomas depends on the age of the patients, the location, or the initial size (possible co-factors/predictor criteria for increase of growth); influence of oral contraceptives (OC).

Methods

Patient records (2010–May 2016) were retrospectively and systematically evaluated in regards to their growth and clinical course. The patients received a follow-up questionnaire by mail about the further history. Linear regression analysis and generalized regression analysis were performed to determine the influence of various factors on the growth of myomas.

Results

Overall, 152 met the further inclusion criteria. Most of the myomas increased in size but 10% of the myomas became smaller without therapy. There is a significant dependency between the initial myoma size, and the first and second measurements, but not between those measures and myoma localization. In regression analysis, there was also a significant association between the growth of the myomas and the initial size but no association with age, complaint symptoms, and use of OC. However, the use of OC waas significantly associated with myoma growth in GEE.

Conclusions

The course of growth of myomas has large variance, so this should not be taken as a sign for a malignant event (sarcoma or the so-called STUMP). The growth takes place with considerable individual variability and ultimately is not predictable.

     

Longitudinal associations of social cognition and substance use in childhood and early adolescence: findings from the Avon Longitudinal Study of Parents and Children

Substance use is associated with impaired social cognition. Experimental studies have shown that acute intoxication of alcohol, tobacco, and cannabis decreases the performance in non-verbal, social communication and theory of mind tasks. However, in epidemiological studies the temporal direction of this association has gone relatively unstudied. We investigated both directions of association within an adolescent birth cohort: the association of social cognition with subsequent substance use, and the association of early substance use with subsequent social cognition. We used data from the Avon Longitudinal Study of Parents and Children, a UK birth cohort. Logistic regression indicated that poor childhood non-verbal communication was associated with decreased odds of adolescent alcohol (OR 0.70, 95% 0.54–0.91), tobacco (OR 0.62, 95% CI 0.47–0.83), and cannabis use (OR 0.62, 95% CI 0.46–0.83). Early adolescent substance use was associated with increased odds of poor social communication (alcohol: OR 1.46, 95% CI 0.99–2.14; tobacco: OR 1.95, 95% CI 1.33–2.86) and poor social reciprocity (alcohol: OR 1.57, 95% CI 1.18–2.09; tobacco: OR 1.92, 95% CI 1.43–2.58; cannabis: OR 1.54, 95% CI 1.16–2.05). Overall, the relationship between social cognition and substance use was different in each temporal direction. Poor non-verbal communication in childhood appeared protective against later substance use, while adolescent substance use was associated with decreased social cognitive performance.