Diabetes was induced in 24 adult male Wistar rats by a single intravenous injection of streptozotocin. The ultramorphology of the coronary arterial wall was studied by scanning and transmission electron microscopy up to 10 weeks following this diabetes induction. At that moment, several ultrastructural characteristics of primary atherogenesis could be observed, i.e. important myointimal thickening with extensive medial smooth muscle cell migration towards and into the intima, and synthesis of an abundant mass of intercellular ground substance in the media and in subendothelial areas. Lipid deposition or foam cell formation was not observed. These results confirm that experimental diabetes is a risk factor for the coronary arterial wall as it induces typical atherogenic phenomena.

Aging↗

PubMedDate not supplied

A revised interpretation of the TRH test results in female depressed patients. Part I: TSH responses. Effects of severity of illness, thyroid hormones, monoamines, age, sex hormonal, corticosteroid and nutritional state.

Thyrotropin secreting hormone (TSH) levels were recorded in baseline conditions and 20 and 60 min after thyrotropin releasing hormone (TRH) administration (200 micrograms i.v.) in 60 depressed females categorized according to DSM-III. Basal TSH (TSHB) and peak TSH responses (TSHP) were measured using ultrasensitive RIA assays. The use of delta max TSH (TSHP minus TSHB) had no advantage over the use of TSHP since both factors were almost linearly (r = 0.98) correlated. TSHP was largely (72% of the variance) predicted by TSHB. It was suggested that TSHP consisted of two components. The first part was a relative deduction from TSHB. The second part was the newly proposed concept of the residual TSH (TRHR). This part was computed by partialling out the relative effects of TSHB on TSHP by means of regression analysis. In clinical practice two relevant factors should be used to evaluate the hypothalamic-pituitary-thyroid (HPT) axis: (1) TSHB reflecting the setpoint of the HPT axis and (2) TSHR reflecting the latent capacity of the HPT axis to respond to overwhelming amounts of exogenous TRH. TSHB was significantly reduced in severely depressed patients (296.X3, 296.X4) as compared with minor depressives (300.40, 309.00). These differences could be attributed to significantly increased free thyroxine levels and to noradrenergic hyperactivity in the severely depressed females. TSHR correlated significantly and negatively with follicle stimulating hormone levels, age, body mass index and the post-dexamethasone cortisol values. TSHR was significantly reduced in the post-menopausal state.

Adult↗

PubMedDate not supplied

A revised interpretation of the TRH test results in female depressed patients. Part II: Prolactin responses. Relationships with sex hormones, corticosteroid state, age, monoamines and amino acid levels.

Prolactin (PRL) levels were recorded in baseline conditions and 20 and 60 min after thyrotropin releasing hormone (TRH) administration (200 micrograms i.v.) in 60 depressed females categorized according to DSM-III. Peak PRL responses were significantly (r = 0.727, P less than 0.001) correlated with their baseline levels. Consequently, the PRL responses to TRH were largely predicted by baseline PRL levels. It was suggested that the PRL responses to TRH consisted of two parts. The first component was a relative exaggeration of basal PRL, reflecting the basal activity of the hormone. The second component was the residual response. This part was estimated by partialling out the relative effects of basal PRL on peak PRL responses by means of regression analysis. Basal PRL and residual PRL responses were uninformative for major depression. Post-menopausal females showed significantly reduced basal PRL levels. There was a significant negative correlation between basal PRL and follicle stimulating hormone levels, age and post-dexamethasone cortisol values. The residual PRL responses were negatively correlated with free triiodothyronine levels and positively with serotonergic variables, i.e., 5-hydroxyindoleacetic acid in 24-h urine and the ratio L-tryptophan/competing amino acids.

Adult↗

PubMedDate not supplied

PCNA, Ki-67 and hTERT in residual benign meningiomas.

BACKGROUND: Relapse in individual patients after incomplete/residual removal of meningiomas cannot be predicted by histology alone as re-growth occurs even in histologically benign meningiomas. MATERIALS AND METHODS: Proliferating cell nuclear antigen (PCNA), Ki-67 and human telomerase reverse transcriptase (hTERT) labelling indices were measured in histological sections derived from residual meningiomas in 37 patients to assess their relationship to relapse. The labelling index (LI) expressed the percentage of tumour cell nuclei immunoreactive for PCNA, Ki-67 or hTERT in 1,000 tumour cells counted per section. The histological specimens comprised the following 2 groups: (i) stable for at least 10 years after initial partial resection of residual meningiomas: 20 specimens; (ii) relapsing between 11 and 145 months after initial resection of residual meningiomas: 17 specimens. RESULTS: The proliferative activity and hTERT expression do not directly correlate with every relapse. The PCNA LI significantly differed in the relapsing group (10.8%) compared to the stable group (5.5%) (p=0.08). The Ki-67 LI also was higher in the relapsing group (2.5%) than in the stable group (2.0%), but not statistically significantly (p=0.9). hTERT LI was significantly higher in the relapsing group (27.8%) than in the stable group (7.2%) (p<0.01). CONCLUSION: The mean PCNA, Ki-67 and hTERT LI were higher in the relapsing group of residual meningiomas than in the stable group, although no statistical difference was found for PCNA and Ki-67. On the other hand, a statistical difference between the two groups of meningiomas was found for hTERT; however, it is no absolute predictor for relapse at the individual patient level.

Adult↗

PubMedDate not supplied

Telomerase activity and hTERT protein expression in meningiomas: an analysis in vivo versus in vitro.

BACKGROUND: Telomere length maintenance is essential for tumorigenesis. Most human tumours stabilise their chromosome ends by telomerase, a specialised reverse transcriptase that adds telomeric repeats (TTAGGG) to these ends. The main components of this telomerase complex are a reverse transcriptase (hTERT) and an integral RNA component (hTR). Most typical meningiomas, however, do not have active telomerase, although some express the hTERT component. The aim of this study was to evaluate telomerase activity and its reverse transcriptase for 33 (30 typical and three atypical) meningiomas in vivo and in vitro. MATERIALS AND METHODS: Telomerase activity was examined by the telomeric repeat amplification protocol (TRAP) assay. The protein, telomerase reverse transcriptase, was visualised by immunohistochemistry. RESULTS: In vivo, telomerase activity was detectable in one out of 30 typical meningiomas and in two out of three atypical meningiomas. hTERT protein expression in vivo was positive in 14 out of 33 (42%) cases. The mean percentage of positive nuclei was 12.9% (SD=21.0). In vitro, 22 out of 33 (66%) meningiomas were positive for hTERT, with a mean percentage of positive nuclei of 31.8% (SD=37.1). Only four expressed telomerase activity in vitro, from which three had expressed telomerase activity in vivo. A significant association was found for telomerase activity (p<0.001) and hTERT expression (p<0.001) in vivo versus in vitro; a significant association was found for hTERT expression and telomerase activity in vivo (p<0.05) and in vitro (p<0.05). CONCLUSION: The results of our study suggest that hTERT expression is an early event in carcinogenesis in contrast to telomerase activity. Fast-proliferating hTERT-positive tumour cells may overgrow in vitro by clonal selection.

Adult↗