Showing papers by "University of Florence published in 1987"

The genetic defect causing familial Alzheimer's disease maps on chromosome 21

Abstract: Alzheimer's disease is a leading cause of morbidity and mortality among the elderly. Several families have been described in which Alzheimer's disease is caused by an autosomal dominant gene defect. The chromosomal location of this defective gene has been discovered by using genetic linkage to DNA markers on chromosome 21. The localization on chromosome 21 provides an explanation for the occurrence of Alzheimer's disease-like pathology in Down syndrome. Isolation and characterization of the gene at this locus may yield new insights into the nature of the defect causing familial Alzheimer's disease and possibly, into the etiology of all forms of Alzheimer's disease.

Solar wind diagnostics from Doppler-enhanced scattering

Abstract: Solar wind ions can attain sufficient outflow speed, w, to cause line excitation by chromospheric or transition region radiation in a nearby line. It is shown that this extends the diagnostic possibilities of a coronal EUV line to much larger values of w than would be possible if pumping were limited to radiation from the same spectral line. For the 1037.6 A coronal line of O VI, the pumping effect of the chromospheric C II 1037.0 A line is efficient for w between 100 and 250 km/s. An approximate expression for the line ratio for a doublet of the Li or Na isoelectronic sequences is derived, and the diagnostic capabilities of doublet line ratios, either by themselves or combined with the observation of other quantities, are discussed. In particular, that the determination of doublet line ratios at several heights can be sufficient to yield the solar wind velocity at those heights together with a constraint on other coronal parameters.

Growth conditions and regularity, a counterexample

Abstract: It is shown that the so-called growth conditions are “necessary” for the local regularity of minimizers.

Absence of duplication of chromosome 21 genes in familial and sporadic Alzheimer's disease

Abstract: The possibility that Alzheimer's disease (AD) is caused by overexpression or duplication of one or more genes on chromosome 21 has been raised by the observation of AD-like neuropathologic changes in individuals with Down syndrome and by the mapping of both the defect for familial AD and the amyloid beta protein gene to this autosome. Possible duplication on chromosome 21 was investigated in both familial and sporadic AD by means of restriction fragment length polymorphisms for the amyloid and SODI loci, as well as for DNA markers in the vicinity of the familial AD defect and in the critical Down syndrome region of chromosome 21. No evidence of increased DNA dosage was observed in either brain or leukocytes of patients with inherited or sporadic forms of AD. Duplication of these regions is therefore not a frequent event in either form of AD. Furthermore, no significant allelic association was detected between AD and any of the loci, including the amyloid and SODI genes, providing no support for the hypothesis that defects in these specific genes are the primary cause of AD.

Unmasking latent dysnociception in healthy subjects.

Abstract: SYNOPSIS Headache is the most common side effect of nitroglycerin, administered for angina pectoris. Two phases can be distinguished in nitroglycerin-induced headache: the first phase (immediate headache), a mild sensation of temporal pulsating pain, can be due, at least in part, to the vasodilation provoked by nitroglycerin; the second phase (delayed headache), an increasing pain, possibly with nausea and vomiting, lasting even for a number of hours, is independent from the vasomotility, since it arises and persists when all vasomotor and metabolic nitroglycerin-induced changes are over. The present investigation demonstrates that healthy subjects, neither suffering from idiopathic headache nor with a family headache history, never complain of delayed headache after nitroglycerin; healthy subjects not suffering from headache but who have one or both parents suffering from migraine, exhibit the delayed long-lasting headache in 28.6% of cases; finally, 66.7% of their migrainous parents complain of the delayed long-lasting headache after nitroglycerin. The following conclusions can be drawn: nitroglycerin-induced delayed headache 1) is not a true side effect of nitroglycerin, since it is never present in healthy subjects; 2) is peculiar to migraine sufferers: or 3) is an index of migraine predisposition, as it may be present in healthy subjects, but only if they have one or two migrainous parents. The features of nitroglycerin-induced delayed headache suggest an analogy with the phenomenon of overreaction, a painful and exaggerated response (in latency, intensity and duration) to a stimulus, that is the most typical aspect of central pain. In nitroglycerin-induced delayed headache, which shows close similarities to the spontaneous attack of migraine, the trigger stimulus could be the moderate immediate headache which is probably correlated with the vasodilation provoked by nitroglycerin.

Hypohidrotic ectodermal dysplasia

Abstract: The authors report a case of Hypohidrotic ectodermal dysplasia (Christ-Siemens-Touraine syndrome). Diagnosed at the age of 2 months.

Interactions between oxiracetam, aniracetam and scopolamine on behavior and brain acetylcholine.

Abstract: The effect of cognition-enhancing agents oxiracetam and aniracetam on scopolamine-induced amnesia and brain acetylcholine decrease was investigated in the rat. Acetylcholine levels were measured by means of a gas-chromatographic method. Scopolamine (0.63 mg/kg IP 60 min before training) prevented the acquisition of a passive avoidance conditioned response ("step through": retest 30 min after training) and brought about a 64, 56 and 42% decrease in acetylcholine level in the cortex, hippocampus and striatum respectively. Oxiracetam (50 and 100 mg/kg IP) administered 30 min before scopolamine reduced the scopolamine-induced amnesic effect and decrease in acetylcholine level in the cortex and hippocampus, but not in the striatum. Lower and higher doses of oxiracetam were ineffective. Aniracetam (100 mg/kg PO) also prevented scopolamine-induced amnesia but attenuated acetylcholine decrease in the hippocampus only. Aniracetam (300 mg PO) reduced acetylcholine decrease in the hippocampus but did not prevent scopolamine-amnesia. In conclusion, oxiracetam and aniracetam exert a stimulatory effect on specific central cholinergic pathways. However, a direct relationship between cognition-enhancing properties and cholinergic activation needs further confirmation.

Characterization of cells from invaded lymph nodes in patients with solid tumors. Lymphokine requirement for tumor-specific lymphoproliferative response.

Abstract: The specific immune response against the malignant cells was investigated in patients with urinary bladder or larynx cancer. Lymphocytes from lymph nodes that drain the tumor site were tested for their proliferative and cytotoxic capacities against autologous malignant cells isolated from the primary tumor. In no occasion was a proliferative or a cytotoxic response observed. However, when the lymph node cell suspensions were depleted of cells expressing both OKM1 and Leu-7 markers by rosetting with the appropriate mAbs, a proliferative response could be observed. The lymphocytes responded to autologous tumor cells only if IL-2 was added to the cultures. IL-2 alone induced some cell proliferation, which was not, however, comparable to that observed in response to both IL-2 and tumor cells. A panel of allogeneic tumor cells consistently failed to stimulate OKM1-, Leu-7- cells in vitro. Response to autologous tumor cells was not caused by HLA-encoded molecules, as occurs in the autologous mixed lymphocyte reaction, since OKM1-, Leu-7- cells failed to be stimulated by autologous non-T cells. A proliferative response was observed only with cells from lymph nodes that had been classified as invaded by malignant cells according to histopathologic criteria. Cells from noninvaded lymph nodes consistently failed to respond. Cells stimulated with autologous tumor cells could be expanded in short-term lines by continuous addition of IL-2 and malignant cells. One of these lines, which comprised mainly T8+ cells, was stimulated to proliferate only by autologous tumor cells, and its proliferative response was inhibitable by anti-class I and not by anti-class II mAbs. This line showed lytic capacities against autologous malignant targets, while it was inefficient against all of the other allogeneic cells tested. In another set of experiments, the mechanisms whereby exogenous IL-2 had to be added to the cultures to sustain a proliferative response against neoplastic cells were investigated. When cocultured with autologous malignant cells, OKM1-, Leu-7- lymphocytes expressed IL-2 receptors, as could be assessed by anti-Tac fluorescent staining. Under these culture conditions, these cells did not produce IL-2, and no proliferation was observed. Addition of purified IL-1 to the cultures induced IL-2 production and cell proliferation. It is concluded that metastatic lymph nodes contain a T cell population that can be detected in a proliferative assay when both suppressor cells are removed and the appropriate molecular signals are supplied.

Cutaneous lesions in capsaicin-pretreated rats. A trophic role of capsaicin-sensitive afferents?

Abstract: 1. The time course and regional distribution of ‘spontaneous’ cutaneous lesions in rats desensitized to capsaicin as newborns was correlated to behavioural observations and regional distribution of substance P-like immunoreactivity (SP-LI) and tachykinin-like immunoreactivity (TK-LI) in various skin areas. 2. ‘Spontaneous’ skin lesions in the form of wounds, scabs and areas of alopecia were observed in 80–90% of rats desensitized to capsaicin. No major sex-related differences were observed with regard to incidence and distribution of the lesions with the possible exception of a lesser tendency to bilateral lesions in female rats. 3. ‘Spontaneous’ skin lesions were almost restricted to the head: the areas most frequently affected were snouts, periocular and retroauricular regions and ventral area of the neck. 4. No major differences were observed between capsaicin- or vehicle-treated animals in spontaneous or novelty-induced grooming as well as in open-field gross behaviour. Likewise, no differences were observed in the mouse-killing behaviour. 5. Both SP-LI and TK-LI in various skin areas were significantly reduced by systemic capsaicin pretreatment. The rank order of various skin areas for SP-LI or TK-LI levels was: snouts > thigh > neck > abdomen ≃ retroauricular region. 6. Intradermal injection of Arg-neurokinin B, a potent and water soluble derivative of neurokinin B, produced a similar plasma extravasation (Evans blue leakage technique) in the skin of vehicle- or capsaicin-pretreated rats. 7. In capsaicin-desensitized rats fur regrowth (measured at abdominal level, 28 days after shaving) was significantly less than in vehicle-treated animals. 8. The s. c. injection of 1 N HCl in the dorsal thoracic region (an area devoid of ‘spontaneous’ lesions in capsaicin-desensitized animals) produced cutaneous ulcers whose area and depth were greater in capsaicin- than vehicle-treated rats. 9. These findings are consistent with the hypothesis that capsaicin-sensitive nerves play a trophic role in the rat skin and contribute to its ability to react and repair injuries. The most consistent explanation for the restricted localization of ‘spontaneous’ skin lesions to the head seems to be that ‘normal’ injurious factors (such as grooming) operate on a distrophic skin to induce lesions by repeated microtrauma.

Reduced production of interleukin 2 and interferon-gamma and enhanced helper activity for IgG synthesis by cloned CD4+ T cells from patients with AIDS.

Abstract: Purified T lymphocytes (E rosetting cells) isolated from peripheral blood (PB) of four patients with acquired immune deficiency syndrome (AIDS) were cloned under culture conditions (phytohemagglutinin plus interleukin 2) which allow clonal expansion of most T lymphocytes. A total number of 101 T cell clones (37 CD4+ and 64 CD8+) from PB of AIDS patients and of 188 T cell clones (115 CD4+ and 73 CD8+) from PB of four normal controls were obtained and tested for their helper function as well as for their capacity to release lymphokines. Unstimulated CD4+ TCC from patients with AIDS showed enhanced helper function for IgG synthesis in vitro in both autologous and normal allogeneic B cells in comparison to clonable CD4+ T cells of normal donors. Such activity was further potentiated by addition to the cell cultures of anti-CD3 monoclonal antibody. The majority of CD4+ T cell clones from AIDS patients showed a reduced ability to produce interleukin 2 and interferon-gamma in response to activation with phytohemagglutinin. However, most of them released greater amounts of soluble factor(s) able to promote B cell proliferation of anti-IgM-activated normal B cells and to induce the differentiation of normal B lymphocytes into IgG-secreting cells. These data demonstrate that most surviving CD4+ T cells in PB of patients with AIDS belong to a T cell subset producing B cell growth and differentiation factors, which may contribute to the B cell hyperactivation seen in AIDS patients.

Effect of diodes-laser silver arsenide-aluminium (Ga-Al-As) 904 nm on healing of experimental wounds.

Abstract: Diodes-laser silver arsenide-aluminium (Ga-Al-As) 904 nm, which was used because of its properties of good tissue penetration and manageability, applied 5 min daily for 5 days at 3,000 Hz of frequency (energy density = 3 J), promoted healing of experimental wounds in rats from both a microscopic and histologic point of view. The same laser applied in these experimental conditions (number of rats was eight for each group) at the same energy density (3 J) for 10 min daily during 5 days at 1,500 Hz of frequency did not affect the experimental wounds.

Enhanced production of gamma-interferon by thyroid-derived T cell clones from patients with Hashimoto's thyroiditis.

Abstract: T lymphocytes from thyroid infiltrate and peripheral blood (PB) of four patients with Hashimoto's thyroiditis (HT) were analysed at clonal level for their ability to secrete interleukin 2 (IL-2) and gamma-interferon (gamma-IFN). As controls, T cell clones from PB of four normal donors and from spleen of two trauma victims were used. While no abnormality was found in the capacity to produce IL-2, the proportion of gamma-IFN-producing (IFN-P) T cell clones derived from HT infiltrates was significantly higher (P less than 0.0005) than that of IFN-P clones derived from normal or patient PB. Most of CD4+ and CD8+ IFN-P clones from thyroid infiltrates, as well as a proportion of CD4+ PB-derived clones of patients with HT, released higher amounts of gamma-IFN than control clones. A relationship could be demonstrated between high gamma-IFN production and natural killer (NK) activity in T cell clones from thyroid and PB of HT patients. In fact, the percentage of IFN-P clones with NK potential (NK+) was remarkably higher (P less than 0.0005) in thyroid infiltrates than in normal spleen or PB. The proportion of IFN-P NK+ clones from patient PB was also significantly increased (P less than 0.02) but, unlike thyroid-derived clones in which the majority of IFN-P NK+ clones were CD8+, most PB-derived IFN-P NK+ clones from the same patients expressed the CD4+ phenotype. Almost all thyroid NK+ clones could be triggered to produce more gamma-IFN, while gamma-IFN synthesis by NK-negative thyroid clones was comparable to that of control clones. In view of the multiple effects ascribed to gamma-IFN in the cascade of events leading to immune responses, the abnormal potential to gamma-IFN secretion shown by intrathyroidal T lymphocytes may be of importance in the pathogenesis of autoimmune thyroiditis.

Antinociception induced by systemic administration of local anaesthetics depends on a central cholinergic mechanism.

Abstract: 1 The antinociceptive effects of systemically-administered procaine, lignocaine and bupivacaine were examined in mice and rats by using the hot-plate, writhing and tail flick tests. 2 In both species all three local anaesthetics produced significant antinociception which was prevented by atropine (5 mg kg-1, i.p.) and by hemicholinium-3 (1 microgram per mouse, i.c.v.), but not by naloxone (3 mg kg-1, i.p.), alpha-methyl-p-tyrosine (100 mg kg-1, s.c.), reserpine (2 mg kg-1, i.p.) or atropine methylbromide (5.5 mg kg-1, i.p.). 3 Atropine (5 mg kg-1, i.p.) which totally antagonized oxotremorine (40 micrograms kg-1, s.c.) antinociception did not modify morphine (5 mg kg-1, s.c.) or baclofen (4 mg kg-1, s.c.) antinociception. On the other hand, hemicholinium, which antagonized local anaesthetic antinociception, did not prevent oxotremorine, morphine or baclofen antinociception. 4 Intracerebroventricular injection in mice of procaine (200 micrograms), lignocaine (150 microgram) and bupivacaine (25 micrograms), doses which were largely ineffective by parenteral routes, induced an antinociception whose intensity equalled that obtainable subcutaneously. Moreover, the i.c.v. injection of antinociceptive doses did not impair performance on the rota-rod test. 5 Concentrations below 10(-10) M of procaine, lignocaine and bupivacaine did not evoke any response on the isolated longitudinal muscle strip of guinea-pig ileum, or modify acetylcholine (ACh)-induced contractions. On the other hand, they always increased electrically-evoked twitches. 6 The same concentrations of local anaesthetics which induced antinociception did not inhibit acetylcholinesterase (AChE) in vitro. 7 On the basis of the above findings and the existing literature, a facilitation of cholinergic transmission by the local anaesthetics is postulated; this could be due to blockade of presynaptic muscarinic receptors.

Clinical pharmacokinetics of factor VIII in patients with classic haemophilia.

Abstract: Studies of Factor VIII pharmacokinetics in haemophiliacs can be classified into 2 groups depending on whether single-dose or multiple-dose Factor VIII curves are used This review analyses information published so far in both these areas, with particular emphasis on the choice of appropriate models for pharmacokinetic analysis Single-dose studies of Factor VIII kinetics have previously used a wide variety of methods for pharmacokinetic analysis (empirical methods of Factor VIII level prediction, graphical techniques for semilog analysis, 1-compartment and 2-compartment models) However, Factor VIII poses unique problems to the pharmacokineticist because decay curves can be either monophasic (monoexponential) or biphasic (biexponential) for unknown reasons, and because Factor VIII concentrations are generally subject to significant assay error Problems of compartmental analysis that occurred in previous studies are highlighted, and a model-independent non-compartmental approach for analysing Factor VIII curves is proposed To date, fewer data have been published on multiple-dose kinetics of Factor VIII From a clinical point of view, repeated-dose regimens are most commonly required in patients undergoing surgery and in patients with severe bleeding A fairly well defined ‘therapeutic window’ of optimal Factor VIII plasma concentrations has been identified, particularly in surgical patients This fact has spurred research aimed at applying to haemophilia patients the pharmacokinetic dosing methods commonly used for therapeutic monitoring of drugs (eg Bayesian method for dosage individualisation) A few papers have already been published in this field, and this review summarises problems encountered by previous investigators, and evaluates comparatively the pharmacokinetic methods used

Reflex sympathetic dystrophies and algodystrophies: historical and pathogenic considerations

Abstract: This paper reviews the historical development of the concepts of ‘sympathy’ of organs and of the sympathetic nervous system. In particular, the afferent function of the sympathetic system is discussed. The attention is focussed on sympathetic reflex dystrophies, known in some European schools as ‘algodystrophies.’ The pathogenic mechanisms of these affections, especially of causalgia, are discussed, considering the importance of peripheral damage to nerves, lateralisation of pain, ‘mirror phenomena,’ and the relationship between peripheral and central mechanisms of pain.

Species-related variations in the effects of capsaicin on urinary bladder functions: relation to bladder content of substance P-like immunoreactivity.

Abstract: 1. The effect of capsaicin on bladder motility in vivo (urethane anaesthesia) and in vitro, plasma extravasation (Evans blue leakage technique) and content of substance P-like immunoreactivity (SP-LI) of the urinary bladder was investigated in various mammalian species. 2. Systemic capsaicin desensitization (rat and hamster, 50 mg/kg s.c. 4 days before; guinea-pig 55 mg/kg s. c. 4–7 days before) increased bladder capacity in rats and guinea-pigs and reduced voiding efficiency in guinea-pigs. All other urodynamic parameters were unaffected in both rats, guinea-pigs and hamsters. 3. Reflex bladder voiding was abolished by spinal cord transection in anaesthetized rats and hamsters. On the other hand, hexamethonium-(20 mg/kg i.v.)sensitive voiding contractions were obtained in response to saline filling 45 min from cord transection in guinea-pigs, indicating a profound interspecies variation in the basic organization of micturition. 4. Exposure to capsaicin (1 μM) produced a contraction of the isolated bladder from rats, guinea-pigs (dome) and mice. Capsaicin produced only a slight contractile response in the guinea-pig bladder base. The motor response to capsaicin of the rat, guinea-pig and mouse bladder exhibited marked desensitization, suggesting a specific effect on sensory nerves. On the other hand, capsaicin (1 μM) produced a slight relaxation of the hamster isolated bladder but this effect was reproducible at 1–2 h intervals, suggesting an unspecific effect. Capsaicin (1–10 μM) did not affect motility of strips from the dome or the base of the rabbit bladder. 5. Intravenously administered capsaicin produced a marked plasma extravasation (Evans blue leakage) in the lower urinary tract of rats, mice and guinea pigs. In rats but not guinea-pigs the reaction in the bladder base was greater than in the dome. In hamsters intravenous capsaicin failed to induce any significant Evans blue leakage in the lower urinary tract. 6. SP-LI was detected in the lower urinary tract of rats, guinea-pigs, rabbits and mice but not hamsters. Bladder SP-LI was depleted by systemic capsaicin desensitization in rats, guinea-pigs and mice. Reverse phase HPLC indicated that all the immunoreactive material co-eluted with authentic substance P or its oxidized form. 7. These findings indicate that noticeable species-related differences exist with regard to the functions mediated by the Capsaicin-sensitive neurons in the urinary bladder.

Comparative Study of Interstitial Cells of Cajal

Abstract: The cells present in the alimentary canal, contacting both nerve endings and smooth muscle cells and named interstitial cells of Cajal, show different ultrastructural features. A comparative study has been performed in order to see if these differences can be related to the animal species studied or to the interstitial cell localizations inside the muscle wall of the various levels of the alimentary canal or to their contacts with other cells. Only mammals were considered, and rat, mouse, hedgehog and man have been studied. All the localizations where interstitial cells of Cajal have usually been found were considered: esophagus (body and lower sphincter), stomach (gastric extent of the lower esophageal sphincter, fundus and corpus), small intestine and colon. From this comparison a correlation was found between the morphology and the location of interstitial cells. On the contrary, the morphological differences existing between animal species do not seem to be that consistent. Moreover, the number of contacts between interstitial cells and between these and smooth muscle cells and nerve endings varies according to the interstitial cell location and morphology. It is concluded that the chain nerve endings----interstitial cells of Cajal----smooth muscle cells is not morphologically identical at each gastrointestinal level, and this finding is considered very important in interpreting the role played by the interstitial cells of Cajal in gastrointestinal motility.