Biomedical subjects
Publications and source records attributed to G Palladini.
Amico Bignami, neuropathologist and neuroscientist, professor of Neuropathology at Harvard Medical School, died on August 5, 1994. He is best known for his pioneering work on spongiform encephalopathies and intermediate filaments, in particular glial fibrillary acidic protein (GFAP).
The effects of testosterone (T), dihydrotestosterone (DHT) and methyltrienolone (R 1881) on cell proliferation of eight human pituitary tumors in culture wre assessed by [3H]thymidine incorporation and compared to those of progesterone (Pg) and 17 beta-estradiol. Receptors for androgens (AR), estrogens (ER) and progesterone (PgR) were characterized. AR had a significant inhibitory effect on all AR-positive tumors, whatever their hormonal content. Inhibitory effects of either T and DHT < R1881 < Pg were observed in tumors co-expressing AR and PgR. The inhibitory effect of R 1881 on a PgR-positive/AR-negative tumor suggested that R 1881 action was partially PgR-mediated. The effects of either T or the nonaromatizable DHT and R 1881 were unrelated to ER expression. We conclude that AR can modulate the growth of human pituitary tumors through direct receptor-mediated intracellular pathways which may be common to various pituitary cell types.
Several studies reported that the annual incidence of stroke in patients with sick sinus syndrome ranges from 6 to 10% while the incidence of stroke in patients with atrial fibrillation is about 2-4% and about 0.1% in the normal population. We evaluated the prevalence of cerebral ischemia and peripheral embolism and investigated the predictor factors in a population of 80 patients paced for sick sinus syndrome. The implanted pacemakers were 40 ventricular and 40 physiological stimulation mode was based on the physicians judgement. All patients had cerebral computed tomography scan at the time of implant and after 24 months. Statistical analysis included log-rank test and actuarial curve calculated with Mantel-Haenszel method. At the end of follow-up the end-point occurred in 15 patients: 2 patients had asymptomatic cerebral infarction, 2 had fatal stroke, 2 developed peripheral embolysm, 1 to the lower limb and 1 abdominal; in 4 patients a transient ischemic attack occurred, in 2 a minor stroke and in 3 a non invalidant stroke. No statistically significant difference was found among the subgroups; with different pacing modality. In conclusion, multivariate analysis underlines the role of age > 65 years, history of cerebral ischemia, low atrial ejection force and spontaneous echo contrast in the development of embolic episodes.
OBJECTIVE: To determine the accuracy of ultrasonography (US) vs magnetic resonance imaging (MRI) in the detection of undescended nonpalpable testis. DESIGN AND SETTING: A clinical, radiological, and surgical study was undertaken in boys with undescended nonpalpable testes at Pavia and Milan (Italy) University Hospitals. PARTICIPANTS: Seventeen patients with undescended nonpalpable testes aged 10 months to 14.5 years who were examined between 1989 and 1993. A total of 22 nonpalpable testes were examined using US and MRI techniques. Twenty-one testes were explored surgically. RESULTS: The US located 13 (62%) of 21 testes, 12 of which were found at surgery while one (5%) proved to be false positive. Eight (38%) of 21 evaluations were negative; four (19%) were true-negative results. Of the 12 gonads correctly localized with US, two (17%) were located near the internal inguinal ring while 10 (83%) were within the inguinal canal. The MRI examination located 11 (52%) of 21 gonads, all found at surgery. Of the 10 negative results (48%), five (24%) were false negatives and five agenetic testes (24%) were not found surgically. Of the 11 testes correctly localized using MRI, four were located in the abdomen or just proximal to the internal inguinal ring and seven were in the inguinal canal. Five of the six high testes were correctly localized using US and MRI (two using US and four using MRI). CONCLUSIONS: Neither US nor MRI is currently sensitive enough to stand alone as a screening modality for a nonpalpable testis since the two techniques used separately gave a useful result in 16 (76%) of 21 testes. They appear to be complementary since their combined specificity compared with surgical findings was 95%. Since the localization of an undescended testis is important for planning surgical strategy, US should be used for screening evaluation, and if it is not successful, it should be followed (before any invasive diagnostic procedure) by MRI, which appears to be more reliable in the localization of undescended, high, and "functioning" testes.
Six human pituitary adenoma cultures, characterized for estrogen and progesterone (Pg) receptors, were treated with 17 beta-estradiol (17 beta-E2), Pg and tamoxifen (TAM) at different concentrations, alone and in combination, for 2, 4 and 8 days. Cell proliferation data showed in most cases a stimulating effect of 17 beta-E2 and an inhibitory effect of Pg on cell growth, which appeared to be correlated with specific receptor expression, but independent of pituitary cell hormone content. A marked inhibitory effect of TAM on cell proliferation was present in all cases, but, on the contrary, was independent of estrogen receptor expression.
In the attempt to define possible causes of false positive GH deficiency, the role of caloric intake on GH determination was explored. The serum GH responses to insulin-induced hypoglycemia or arginine were assessed before and after 3 days of a hypocaloric diet in 23 prepubertal children of normal weight, aged 6.7-11.9 yr. Seventeen had short stature and a GH response to insulin and arginine below 10 micrograms/L, and 6 controls had normal stature and a GH peak above 10 micrograms/L in response to arginine. After diet, the serum peak GH and the area under the curve increased in both the patients (P < 0.0005 and P < 0.0005) and the controls (P < 0.005 and P < 0.025) with a GH peak greater than 10 micrograms/L in 11 of 17 patients. The patients with a persistent GH response below 10 micrograms/L also had lower mean 12-h overnight GH levels (P < 0.0005), whereas those with a normal GH response after diet had an overnight GH level greater than 3 micrograms/L. In the patients, the mean nighttime GH concentrations correlated with the serum GH peak (r = 0.85; P < 0.005) and with the area under the curve after the diet (r = 0.65; P < 0.025). The diet induced changes in plasma insulin-like growth factor-I, GH-releasing hormone levels, basal blood sugar and the nadir level obtained during insulin stimulation, total T3, and rT3. Height increased significantly during 1 and 2 yr (P < 0.005) of GH treatment only in patients with a GH response below 10 micrograms/L after the diet. These data are consistent with the hypothesis that the GH response to stimulation is strongly calorie dependent and that 3 days of a hypocaloric diet can increase the number and height of GH peaks and the total GH responses to insulin and arginine. The clear correlation of the GH response to stimulation after a hypocaloric diet with the mean nighttime GH and also with the growth response to GH treatment indicates that GH deficiency may be overdiagnosed in many children with short stature.
The abortive axonal regeneration in the central nervous system (CNS) of mammals has been attributed to a series of inhibitory factors. Previous reports suggest the development of autoimmune reactions following CNS lesion in mammals. In this study we investigated whether immunosuppressive treatment with cyclosporine A is able to facilitate axonal regeneration in rats submitted to complete transverse section of the spinal cord at the level of T7-T8. Treated animals received daily subcutaneous injections of cyclosporine A (2.5 mg/kg), while control rats were given a similar treatment with saline. Immunosuppression was begun immediately after spinal cord transection. Strong evidence of morphological axonal regeneration was observed 15 days after surgery in all cyclosporine A treated animals. Furthermore, treatment with cyclosporine A markedly reduced the seric immune reaction elicited by the lesion. The results of this study, although preliminary, provide further evidence for the development of autoimmune processes following lesion in the CNS, and suggest that blocking of the immune reaction facilitates axonal regeneration in the rat.
We report the intra vitam histopathological findings on the brain of a female patient presenting an adult form of orthochromatic leukodystrophy. At 38 years of age the patient began to show progressive dementia and a pseudobulbar syndrome. The pedigree revealed an autosomal dominant pattern of inheritance. The CT scan showed a wide hypodensity of the anterior white matter. Biochemical investigations showed only a slight elevation of serum VLCFA and no alteration of urinary enzymatic activities. Cortical and subcortical biopsy specimens from the right frontal lobe showed: neuronal loss in the gray matter, accumulation of autofluorescent material within residual neurons and sudanophilic material within macrophages and astrocytes, sparing of axons. Electron microscopy showed lamination and fragmentation of the myelin and the presence of electrondense bodies and vesicular material into oligodendrocytes and astrocytes. We discuss the differential diagnosis of OLD forms with adult onset, namely between Löwenberg-Hill disease and the pure form of OLD with pigmented glial cells.
Primary cultures of rat hepatocytes were used to study the effects of the flavonoids diosmin and its main metabolite diosmetin on the cell membrane damage caused by erythromycin estolate (EE) and oxidative stress caused by tert-butylhydroperoxide (TBHP). The damage was evaluated by the leakage of intracellular enzymes lactate dehydrogenase, aspartate-aminotransferase and the residual cell content of a lysosomal marker acid phosphatase (AP). After treating the cells for 40 h with diosmetin EE induced less enzyme leakage. The content of AP was kept higher by diosmetin pretreatment after 6 h exposure to EE. Diosmin at the same concentrations had barely any effect. Diosmetin, but not diosmin, also protected against TBHP toxicity and this was related to lower lipid peroxidation and higher glutathione content caused by pretreatment with the flavonoid. When the cells were treated simultaneously with TBHP and diosmetin after 21 h of culture, the protection by the flavonoid was even higher. In fact the antioxidant activity of diosmetin was considerably greater than that of diosmin. After 40 h exposure to both flavonoids diosmin but not diosmetin was detectable in the cell membrane fraction, suggesting that the latter's protective effect is associated with its metabolites.
Ninety-four cryptorchids, 50 monolateral and 44 bilateral, aged from 2-9.4 yr (mean, 5.1 +/- 0.5 yr), were studied for the hormonal and immunogenetic profile. Pituitary-gonadal function was studied by evaluation of basal and peak GnRH-stimulated serum FSH and LH. In 83 cases, the serum testosterone (T) level was measured before and after CG treatment. No significant differences, between patients and age-matched controls, were found in either FSH or LH levels, whether under basal conditions or after GHRH stimulation. The mean basal serum T level was similar in mono and bilateral cryptorchids and in controls but, on the 15th day after treatment, it was significantly lower in the bilateral cryptorchids (P less than 0.05). CG administration led to testicular descent in 42 patients (23 with monolateral and 19 with bilateral cryptorchidism) and failed in 41 (21 with monolateral and 20 with bilateral cryptorchidism), independently of T increase. Immunogenetic investigation demonstrated that HLA-A11 and A23 were significantly overrepresented in the whole group of cryptorchids in comparison with the controls (P = 0.004 and P = 0.0123, respectively). HLA-A11 was more common in the bilateral form (P less than 0.05), whereas HLA-A29 was more frequent in the monolateral one (P less than 0.05). Forty percent of the bilateral cryptorchids with unsuccessful treatment had the HLA-A11 allele (P less than 0.01) and 70% the HLA-DR5.
Pharmacokinetic studies of diosmin were performed after an oral administration to healthy volunteers. Diosmin and its aglycone, diosmetin, were determined by HPLC and LC-MS techniques. At least, at the level of sensitivity of our method, no parent compound was present in the plasma but only its aglycone, diosmetin. Analysis of the pharmacokinetic parameters showed that the drug was rapidly absorbed. Diosmetin presents a long plasma elimination half-life ranging from 26 to 43 hours. Our data show the total absence of urinary elimination for both diosmin and its aglycone diosmetin, while its minor metabolites are eliminated in the urine, mainly as glucuronic acid conjugates. The presence of degradation products such as alkyl-phenolic acids confirms a metabolic pattern similar to other flavonoids.
The trigeminal ganglion, roots and the initial portion of the ophthalmic, maxillary and mandibular nerves were dissected in 3 cadavers, to study the number, area and composition of the fascicles, and the density and diameter spectra of myelinated fibers. The total number of fibers (x 1000) was 26 in the ophthalmic, 50 in the maxillary, and 78 in the mandibular division, 7.7 in the motor root and 170 in the sensory root. In all nerves, the histograms of fiber diameter had a bimodal distribution. Cutaneous and muscle nerve fascicles clearly differed in the fiber density and diameter. The ophthalmic and maxillary nerves (cutaneous) had similar fascicles, and their maximum fiber diameter averaged 14.5 microns. Most fascicles of the mandibular nerve (probably cutaneous fascicles) closely resembled those of the ophthalmic and maxillary nerves, but in some fascicles (probably muscle nerves) the fibers were larger, with a maximum diameter of 19.3 microns. The findings in the three peripheral divisions agree with electrophysiological data about sensory and motor conduction in human trigeminal nerves. The observation that the ophthalmic and maxillary nerves have similar fiber spectra indicates that a special fiber composition does not account for the sparing of the ophthalmic division in trigeminal neuralgia. The absence of very large (A alpha) fibers in the sensory root does not support the view that impulses from muscle spindles are conducted along this root.
In the homeotherms the presence of glial-fibrillary acidic protein (GFAP) and that of neurofilaments (NF) are used as specific molecular markers associated with intermediate filaments (IF) of the glial and neuronal elements respectively. On this basis a comparison was made between trends in the immunohistochemical response to these markers of the ependyma of a both a normal and a regenerating spinal cord in Triturus carnifex (Urodele Amphibian) adults, whose high spinal cord regenerative capacity is due to the ependymal epithelium cells. Under normal conditions, the ependymal cells are vimentin positive and negative for GFAP and the IF, respectively, while GFAP and NF positivity is found in the grey and white matter. During regeneration, by about day 10, vimentin positivity begins to decrease in the ependymal epithelium of the caudal stump and GFAP positive elements appear (subsequently, this was observed also in the ependymal epithelium of the cephalic stump). High GFAP positivity is found also in the newly formed apical ampullae. From day 20 to after day 30 these patterns develop both in the stumps and in the regenerating spinal cord. NF positivity is always restricted to the grey matter alone and to the axonal processes of the white matter. At about day 60, by which time the regenerative processes may be considered as having terminated and the spinal cord has virtually regained its original structure, the immunohistochemical features typical of the rest state are restored in the ependymal epithelium.(ABSTRACT TRUNCATED AT 250 WORDS)
Recent studies have suggested that astrocytes share with the macrophages several properties in vitro, among which is the ability to express MHC Class II molecules and to present some antigens to syngeneic primed lymphocytes (MHC-restricted presentation). It has been claimed in the literature that astrocytes cannot start the presentation and cannot express the related MHC Class II molecules if not previously stimulated with gamma IFN. In this paper we report that 2 human GFAP + glioma cell lines, incubated in culture with various soluble antigens for at least 24 h, were able, in the absence of gamma IFN or of activated lymphocytes, to express the MHC Class II and to expose the antigens on their surfaces. Moreover, when a lysosomotropic agent such as chloroquine was added during the incubation, no MHC Class II expression was observed. This last datum suggests that in astrocytes, as is already known in macrophages, the processing of antigens and their assembling with MHC Class II molecules probably involves the lysosomal apparatus.
The dopaminergic receptors of planaria have been studied with pharmacological and biochemical criteria. Dopamine D1 selective agonists (CY 208243 (10 micrograms/ml) and SKF 38393 (10 micrograms/ml] induced in planaria typical screw-like hyperkinesias, that were inhibited by a D1 antagonist (SCH 23390 (10 micrograms/ml], but not by a D2 antagonist (sulpiride (1000 micrograms/ml]. Dopamine D2 selective agonists (PHNO (5 micrograms/ml), lisuride (5 micrograms/ml] on the contrary induced a typical "C" like curling, that was inhibited by pretreatment with D2 selective blocking agents, but not by D1 selective blocking agents. With agonists with a D1/D2 mixed action (apomorphine 60 micrograms/ml) or with amphetamine (100 micrograms/ml), the D1 type movements appeared to be more evident. Dopamine D1-selective agonists, mixed action agonists or D2-selective agonists, all induced a significant increase in levels of cAMP, that was prevented by pretreatment with the specific DA blocking agent.
After traumatic lesion adult cock spinal cord displays lively axonal regenerative activity. After 22 days, morphological regeneration regresses; functional regeneration is never observed. Before and after spinal lesion in the cocks, IgG decoration of myelin sheaths is never observed. The sera of both injured and intact animals tested both by immunohistochemical methods on intact spinal cord sections and by immunoelectrophoresis on a protein extract of homologous spinal cord are always negative. The authors suggest that the absence in Birds of any autoimmune response against c.n.s. antigens after surgical exposition, as observed in Mammals, is possibly related to the capacity of the central axons to regenerate in Birds, as observed by the Authors in Amphibia and Reptilia (Triturus and Lacerta).
Spinal cord lesion in newt is followed by complete cell and fibre regeneration. Previous observations showed that the presence of a granuloma due to a foreign substance (talcum) in the vicinity of the cut spinal cord slows down and/or prevents regeneration. The present experiments, while confirming previous evidence, show that, in animals with a paraspinal granuloma or a subcutaneous granuloma containing an autoplastic and homoplastic spinal cord implant, immunocomplexes appear on the cut ends as has been observed by the same authors in animals in which spinal cord regeneration does not occur (Mammals). The authors discuss the results in view of their theory of the autoimmune nature of the absence of axonal regeneration.