Secondary allogeneic challenge of xenotransplant recipients.
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Biomedical subjects
Publications and source records attributed to M Ermini.
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Progestasert devices releasing 65 micrograms of [14C]progesterone daily were inserted in 10 women 3 months prior to elective hysterectomy. Following surgery, specimens were examined by light and electron microscopy and by autoradiography. In three uteri, removed during the early follicular phase, there was a clear contrast between the appearance of the superficial portion of the endometrium in the zone immediately adjacent to the device, when compared to areas away from the progestasert. This difference became more pronounced in four specimens obtained at mid-cycle and tended to diminish during the luteal phase: the number of glands was still lower than normal, but stromal decidual reaction was apparent throughout the functional layer of endometrium; in addition, in portions away from the device, glands showed the characteristics of a secretory phase. Progesterone and/or its metabolites were abundant in the superficial epithelium and in the portion of the glands adjacent to the surface; and also well distributed in the stroma and in the capillary walls. Historadiography however, clearly showed that progesterone barely penetrated the deeper portion of the endometrium. This picture does not substantially change during the entire cycle.
The Authors have investigated preneoplastic lesions and the problem of the identification of benign lesions considered with or without preneoplastic potential, comparing for the occasion the presence of transformation markers in these lesions with the positivity of tumor markers in neoplastic tissue. The dosages have been valued on neoplastic tissue (180 cases), dysplastic tissue (50 cases), on cystic fluid (70 cases), and on nipple discharge (80 cases). The data obtained show a marked positivity to the tumor markers and the ionic and hormonal content (K+, Na+ DHEAS, PRL evaluation). The positivity of some lesions, not properly preneoplastic (or atypical) towards some markers of neoplasia could show some differences of great interest between benignity and malignity.
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The number of synapses (Nv), the surface density of contact zones (Sv) as well as the average size (S) of E-PTA stained synapses in the supragranular layer of the dentate gyrus from adult (12 months), old (30 month), and Hydergine-treated old (30 months) rats were measured by using quantitative morphometric techniques. In old animals, Nv and Sv were significantly reduced, whereas S was significantly increased as compared with the values in adult rats. Hydergine (Codergocrine mesylate) treatment of old animals (3 mg/Kg/day for 4 weeks) influenced these three parameters, differentially. The Sv in aged animals receiving Hydergine, relative to that in untreated old rats, was significantly increased; the number and size of synapses in the treated old rats were significantly higher and smaller, respectively, than that in old controls. We interpret the present findings to indicate a modulating effect of Hydergine on the morphological plasticity of synaptic junctions in the dentate gyrus of aged rats.
Regular estrous cycles can be reinitiated in old acyclic female rats by pharmacologic, hormonal, and environmental manipulations. The most responsive acyclic states are persistent vaginal cornification (PVC) and spontaneous pseudopregnancy (SP). However, it is not known if the irregular cyclicity that precedes acyclicity during aging can also be alleviated. We found that transient shortening of estrous cycles follows smear sequences indicative of pseudopregnancy in C57BL/6J mice, aged 9-15 mo, suggesting a role for progesterone. This phenomenon was investigated through a limited model of pseudopregnancy in which intact aging mice with lengthened cycles were given progesterone implants (yielding 70 ng progesterone/ml plasma) that suppressed estrous cycles; upon removal of the implants, cycles were transiently shortened in aging mice. Therefore, we hypothesize that withdrawal from the progesterone elevations associated with SP is the mechanism in shortening subsequent estrous cycles. Effects of central-acting drugs, similar to those used to reinitiate cyclicity in acyclic old rats, were also examined. Hydergine, an ergot mixture with partial dopaminergic and serotonergic agonist activities, suppressed SP when fed to 10- to 12-mo-old, middle-aged mice. Hydergine did not otherwise affect estrous cycle length, prevent PVC, or reinitiate cycling in acyclic PVC mice. Feeding L-dihydroxyphenylalanine to middle-aged mice did not suppress SP, affect estrous cycle lengths, or reinitiate cycles from PVC.
The gastrointestinal tract is known to generate hormonal and neural signals that can affect the endocrine function of the pancreas ("enteroinsular axis"). The physiological circumstances under which this connection is operative are still a matter of debate. We investigated the influence of bile flow on glucose homeostasis in an experimental model of internal biliary diversion. After laparotomy in 2-mo-old rats, bile flow was diverted from the duodenum into the second jejunal loop with the use of a plastic minicannula. Rats in which the cannula was implanted but not connected with the common bile duct (sham operation) and rats receiving no treatment were used as control groups. After surgery, the rats with the biliary bypass weighed 10% less than the controls for 3 wk; afterwards and until 9 mo later, operated and nonoperated animals had similar growth curves. After the operation, fasting plasma glucose concentrations fell significantly in the treated rats compared with both sham-operated and control rats; likewise, the glycemic response to orally administered glucose was lower in the treated group 1 wk after surgery. In contrast, no significant difference was found in either the fasting or the glucose-induced plasma insulin levels. Nine months after surgery, the same three groups of animals received an oral glucose tolerance test, an intravenous glucose tolerance test, and a fasting-refeeding test (24 h of fast followed by standard, mixed feeding for another 24 h). On all three tests, bile-diverted rats showed lower plasma glucose responses than either sham-operated or control rats in the face of essentially similar plasma insulin responses.(ABSTRACT TRUNCATED AT 250 WORDS)
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Antibodies against myosin of the fast long. Dorsi and the slow soleus muscle of rabbits were induced in guinea pigs. With the aid of a new technique, the gel-electrophoresis-derived-enzyme-linked-immunosorbent assay (GEDELISA) it could be shown that they are directed against the heavy and the light chains of fast (M. long. dorsi) and slow (M. soleus) myosin. In the indirect immunofluorescence test each antiserum only stained one population of fibres in five different muscles tested. The single fibres were observed to react only with one of the two types of antisera. The following percentage of fibres showed a positive reaction with the anti-fast myosin serum: M. long. dorsi, 95%; M. psoa maior, 95%, M. psoa minor, 92%; M. tibialis ant., 90%; M. soleus, 15%.
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The problem of developing a geriatric pharmacotherapy is briefly discussed. It is stressed that combined scientific knowledge from biological, clinical and pharmacological research should be used as basis. However, in applied (clinical and pharmacological) gerontology, direct relations to basic experimental gerontology are often avoided, because of its seemingly theoretical character. With some examples, it is pointed out that during the recent past, biological-aging research has gained new knowledge, particularly on skeletal muscle and CNS aging, that can be used in the concept of a specific geriatric pharmacotherapy.
Little information about the possible neurochemical-enzymatic changes occuring during aging of human brain is available. We, therefore, investigated the activity of various enzymes of human brains obtained at autopsy and covering a range from 19 to 91 years. Protein kinase, which mediates the information carried by the second messenger cAMP, does not show age-related changes of basal activity. Cyclic AMP-dependent activation of protein kinase remains nearly constant up to 60 years of life, but undergoes a distinct and progressive decline between 60 and 90 years. In corpus striatum no age-related changes of cyclic AMP-dependent protein kinase activity were observed. The activity of carbonic anhydrase demonstrates in both human cortex and corpus striatum an age-dependent decrease which also begins after the 6th decade of life. These neurochemical changes are similar to morphological and physiological changes occuring in the aging brain. They begin after the 60th year of life.
The influence of aging on the myosin type, and on the fibre composition of both the slowly contracting ("red") M. soleus and the fast ("white") M. longissimus dorsi was examined in the rabbit. For myosin characterization isolated myofibrils were electrophoresed on SDS-polyacrylamide gels, and the fibre pattern within the respective muscles was analyzed with an immunocytochemical method. Antisera against either fast or slow rabbit myosin were collected from guinea pigs after longterm immunization. After incubation of the paraformaldehyde-fixed muscle thin sections the fibres containing either fast or slow myosin could be distinguished from each other by indirect immunofluorescence. The soleus muscles of 1 day old rabbits were composed of 25% slow and 75% fast fibres. In young-adult (5--8 mo.) rabbits the fibres were mostly slow (over 90%), while in old age (4--7 y.) again up to 50% of the soleus fibres contained fast myosin. In contrast, in the longissimus dorsi muscle constantly around 95% of the fibres contained fast myosin. In accordance with the immunocytochemical finding of an increase of fast fibres in the aging soleus muscle, the presence of fast myosin could also be demonstrated electrophoretically. With this method, soleus myofibrils from young-adult animals were observed to contain virtually slow myosin only. No slow, but only fast myosin was identified in SDS-gels of longissimus dorsi myofibrils at all ages. These results are discussed in relation to the well known metabolic alterations occurring in the mammalian skeletal muscle during aging.
After partial digestion with micrococcal nuclease, DNA was extracted from nuclei of cerebral cortex neurons from young (23--36 y.) and old (78--85 y.) humans. The DNA fragments were subjected to gel electrophoresis, and their base-pair content determined. The nucleosomal DNA repeat length was found to increase from 170 (+/- 18) base-pairs in the young group to 199 (+/- 8) base-pairs in the old group. This increase of 29 base-pairs appears to be confined to the linker region of the nucleosomal DNA, since the core-DNA was always found to contain approx. 140 base-pairs. In addition, the amount of nuclear DNA digested by the micrococcal nuclease was observed to vary with age: after 30 min. of incubation at 37 degrees C hydrolysis of up to 80% of the nuclear DNA in the young but only up to 60% in the old neuronal nuclei was achieved. The age-dependent increase in chromosomal DNA repeat length is a direct proof of alterations in the basic chromatin structure with aging. It cannot be decided, however, whether the change in DNA digestibility is dependent on alterations of the chromatin basic structure, its superstructure, or both.
The influence of age on the structure of chromatin of various mammalian cells with modest or terminated mitotic activity has been examined. For this purpose chromatin from dog skeletal muscle, and human neuronal and glial cells, has been incubated together with an exogenous histone phosphokinase and ATP-gamma32P, and the phosphate incorporated into the histones determined. For comparison, also free histone has been phosphorylated. The amount of phosphate incorporated into total histone is 16-18 nmol Pi per mg histone in the case of free histone, and about equal for all cell types and ages. Into chromatin-bound histones only 5.5-8.2 nmol Pi per mg histone are incorporated. The differences between the various cell types and age groups are not significant. The relative phosphate incorporation into the single histone fractions depends on the histone as being free or chromatin-bound. In addition, relative phosphate incorporation into the single fractions of chromatin-bound histones is also cell type- and age-specific. The results permit the conclusion that the chromatin is subject to structural changes in the course of aging.
Lymphocytes of young and old donors are stimulated by phytohemagglutinin (PHA). The 32P-incorporation into the histones which occurs in the early phase after PHA-stimulation is determined. In lymphocytes of old persons the 32P-incorporation in the histones is diminished by about 50% with respect to the cells of young donors. Furthermore, it could be shown that in the histones prepared from old cells the amount of H1 is much increased. It is postulated that, in old age, the other 4 histones are poorly extractable.