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Biomedical subjects

M L Rossi

Publications and source records attributed to M L Rossi.

At least 73 records · Page 4Linked to original sources

Immunohistological study of grumose degeneration of the dentate nucleus in progressive supranuclear palsy.

The grumose degeneration observed in the dentate nuclei of 7 cases of progressive supranuclear palsy (PSP) was studied with a panel of antibodies which included 2 neurofilaments, Tau and ubiquitin. Dentate nucleus neurons were negative with all antibodies except ubiquitin which showed a slightly positive homogeneous pattern of staining. The amorphous material surrounding swollen or normal neurons was strongly positive for neurofilament and subunits and numerous torpedoes were observed in the granular layer of the cerebellar cortex. Our results confirm that grumose degeneration consists in degeneration of terminal axons of Purkinje cells in the dentate nucleus. The positivity of dentate nucleus neurons for ubiquitin may support the concept of synaptic dysfunction between Purkinje cells and dentate nucleus neurons.

Aged↗

Ubiquitin in cerebral amyloid angiopathy.

Immunohistological findings in cerebral blood vessels of 4 cases with cerebral amyloid angiopathy (CAA) were compared with those of 4 Alzheimer's (AD) cases. A panel of antibodies against 2 neurofilament subunits (BF10 and RT97), a microtubule-associated protein (TAU) and ubiquitin were used. CAA cases showed a strong immunoreactivity for ubiquitin in blood vessel wall. Senile plaques (SPs) in CAA cases showed strong ubiquitin positivity but the central amyloid core was negative. AD brains showed immunoreactivity with all antibodies in SPs and neurofibrillary tangles (NFTs); blood vessels were consistently negative for ubiquitin. Control brains showed few SPs and NFTs; these were positive for ubiquitin, but blood vessels were negative. These results indicate that vascular amyloid deposition in CAA and AD may have different pathophysiological mechanisms.

Adenosine Triphosphate↗

Ultraviolet irradiation induced brain oedema in rats. A microgravimetric study.

The cerebral cortex of 36 anaesthetized Wistar rats were exposed to ultraviolet irradiation (UV-I) for 6 min through a 2 x 2 mm left parietal craniotomy. Animals were killed at different times and brains were removed immediately after death. Three consecutive coronal sections were obtained and sampled for gravimetric study. The density of the samples was measured using a continuous gradient of organic solvents. Gravimetric results showed significant differences between brain samples. The irradiated left hemisphere was less dense than the right one, and maximum differences in density were found in the medial coronal section. Grey and white matter oedema in the non-irradiated hemisphere was compared with the irradiated hemisphere. Early and delayed onset of odema was observed in both hemispheres but it was more marked in the irradiated hemisphere. In conclusion, brain oedema induced by ultraviolet irradiation in various animals is also reproducible in rats with all the advantages involved in the use of these experimental animals. Microgravimetric study correlated with topographical analysis using this model may lead to an understanding of some of the dynamic aspects of cerebral oedema.

Animals↗

Rhabdomyolysis and acute renal failure following carbon monoxide poisoning: two case reports with muscle histopathology and enzyme activities.

Two patients with carbon monoxide poisoning are presented, both of whom suffered rhabdomyolysis complicated by acute renal failure. One patient, an attempted suicide, developed a compartment syndrome of the right thigh that required fasciotomy and recovered after a period of hemofiltration and hemodialysis. Muscle biopsy appearances were consistent with partial muscle infarction. The other patient, rescued from a smoke filled room, exhibited raised creatine kinase but no evidence of muscle swelling. He developed anuric renal failure and adult respiratory distress syndrome and died despite maximum intensive care. Muscle biopsy showed early evidence of muscle necrosis. In both cases there was a marked reduction of enzyme activities in the muscle biopsy consistent with metabolic derangement. Although there was a clinical compartment syndrome in the first case, there was no muscle swelling at the time of biopsy or subsequently in the second case. A direct toxic effect of carbon monoxide may thus have been an important mechanism contributing to the muscle necrosis in the second case, although local ischemia may have been an exacerbating factor in the first case.

Acute Kidney Injury↗

Efferent control of posterior canal afferent receptor discharge in the frog labyrinth.

EPSP and spike discharges were intracellularly recorded from 90 afferent fibres of the posterior nerve in the isolated frog labyrinth and the effects of electrical activation of the efferent system were tested. Posterior canal efferent synapses were activated, via an axon reflex, by electrical shocks to the anterior-horizontal nerves. The afferent resting discharge of all fibres tested was affected by efferent stimulation: 39 units were inhibited (43%) and 51 (57%) were facilitated. The efferent system was activated with several stimulation frequencies in the 10-200 Hz range applied for different times (250 ms-10 s). By changing the stimulus parameters, inhibition did not reverse to facilitation or vice versa. Facilitation appeared within the train above a threshold frequency of about 10 Hz. The peak response was readily reached within the first second and then, with long lasting stimulation, a marked adaptation ensued. The increase in firing rate was independent of previous resting activity. The relationship between frequency and facilitatory response is described by a logarithmic function over the 30-200 Hz range tested. At the end of short trains a consistent post-stimulation after-discharge appeared, whose intensity is positively related to stimulation frequency and time. Inhibition was achieved at stimulation rates above 10 Hz, and a post-stimulation rebound discharge was evident, which was linearly dependent on previous stimulation rate. The latency values of both inhibitory and facilitatory effects were measured by taking into account either the EPSP release rate or the spike discharge modifications at all the frequencies tested. Latency proved to decrease exponentially with increasing stimulation time from a minimal value of 3 ms to a maximum of 200 ms, with minor differences between inhibition or facilitation. These long latency values, the presence of a threshold frequency and the stimulus- and frequency dependence indicate that the efferent synapses must be activated repetitively to produce detectable effects on the afferent discharge; this is in line with the discharge pattern of the efferent system fibres physiologically measured in some systems. The present results show that the dual central control of the crista ampullaris of frog posterior canal is potentially capable of setting the receptor population at a variable level of sensitivity to mechanical stimuli, with profound modifications in the canal transfer function and the spike encoding mechanism.

Animals↗

HLA-Dr expression by tumor cells compared with survival in high grade astrocytomas.

Frozen samples from 78 high grade astrocytomas were reacted with a monoclonal antibody directed against HLA-Dr invariant chain. Survival data was obtained for all 78 cases. HLA-Dr was expressed by a proportion of tumor cells in 65/78 (83%). Comparison of the survival of positive and negative cases showed that the difference was not statistically significant (p = 0.4). The relevance of the finding is discussed in the context of the immunoreaction to brain tumors.

Antigens, Neoplasm↗

The monocyte/macrophage infiltrate in 35 medulloblastomas: a paraffin-wax study.

We have studied formalin fixed, paraffin-wax embedded tissue from 35 medulloblastomas, collected over 23 years (27 non-desmoplastic and 8 desmoplastic) with KP1 and Mac387 two monoclonal anti-monocytes/macrophage (M/Ms) antibodies recommended for use on paraffin wax embedded tissue. In non-desmoplastic medulloblastomas, outside areas of necrosis, M/Ms were detected in 50% of cases with KP1 and 52% with Mac387. M/Ms were seen in 100% of desmoplastic medulloblastomas with both antibodies. Semiquantitative assessment revealed that, on average, desmoplastic tumors had at least three times as many infiltrating M/Ms as non-desmoplastic tumors. There was no significant difference in the findings with the two antibodies or, between recently embedded and "older" tumors. The findings may be indicative of the presence of a host M/Ms immune response in medulloblastoma, which may be more accentuated in desmoplastic medulloblastomas. Furthermore, we conclude that these antibodies are quite suitable for the study of infiltrating M/Ms, thus lessening (but not obviating) the need for frozen tissue for immunohistological studies.

Antibodies, Monoclonal↗

Differentiation in embryonal neuroepithelial tumors of the central nervous system.

Ninety-six embryonal neuroectodermal tumors were studied histologically and immunohistologically with a panel of antibodies including glial, neuronal, epithelial, mesodermal, and myelin markers. In 71 tumors there was glial and neuronal differentiation and expression both of an S (photoreceptor) antigen and vimentin. In five tumors there was only glial differentiation and in 20 tumors only neuronal differentiation. No reactivity for myelin and epithelial markers was found. Histologic and immunohistologic findings identified various degrees of differentiation in different tumors, which was bipolar (glial and neuronal) in most tumors and unipolar in the remainder. The authors suggest that their findings may be the result of normal or aberrant oncogenic differentiation, agreeing with the nomenclature of the World Health Organization classification for these tumors with and the inclusion of a category for ependymoblastoma.

Adolescent↗

Brain lesions following combined treatment with methotrexate and craniospinal irradiation.

Eight patients with meningeal seeding by carcinoma or lymphomas were treated with intravenous (i.v.) and/or intrathecal (i.th.) Methotrexate (MTX). Seven patients received additional craniospinal irradiation and in all seven a fatal encephalopathy developed. On the bases of clinical and morphological findings we identified an acute and a delayed form of encephalopathy and concluded that the concurrent administration of Methotrexate and of craniospinal irradiation increases considerably the risk of brain damage.

Adult↗

Topographical localisation of endothelin mRNA and peptide immunoreactivity in neurones of the human brain.

The distribution of endothelin mRNA and immunoreactivity in the human brain was investigated using the technique of in situ hybridization and immunocytochemistry. Cryostat sections from 22 cases of neurologically normal adult human brain, collected 3-7 h post-mortem were hybridized with 35S-labelled complementary (c)RNA probes prepared from the 3' non-coding region of endothelin-1 cDNA, and the chromosomal genes encoding endothelin-2 and -3. In situ hybridization with all three cRNA probes revealed labelled neuronal cell bodies in laminae III-VI of the parietal, temporal and frontal cortices. Labelled cells were also seen, scattered throughout the para- and periventricular, supraoptic and lateral hypothalamic nuclei, the caudate nucleus, amygdala, hippocampus, basal nucleus of Meynert, substantia nigra, raphe nuclei, Purkinje cell layer of the cerebellum and in the dorsal motor nuclei of the vagus of the medulla oblongata. The distribution of neurones immunoreactive to endothelin was similar to that of endothelin mRNA, although fewer immunoreactive cells throughout the brain, were noted. Immunoreactive fibres were present mainly in the cortex and hypothalamus, and to a lesser extent in the brain stem. Combined in situ hybridization and immunocytochemistry on the same section revealed the presence of endothelin-1 mRNA and immunoreactivity in the same cortical neuronal cell. Colocalisation studies in the cortex revealed endothelin-1 mRNA and immunoreactivity in a number of cells which also expressed neuropeptide Y mRNA and immunoreactivity. In the hypothalamus and basal nucleus of Meynert endothelin immunoreactivity was colocalised to a subset of neurophysin- and galanin-immunoreactive cell bodies respectively. Endothelin mRNA and immunoreactivity was also seen in some blood vessel endothelial cells. The findings of endothelin mRNAs and immunoreactivity in heterogenous neuronal populations further emphasises the potential role of endothelin as a neuropeptide, probably having diverse actions in the nervous system of man.

Adult↗

Characterization of the mononuclear cell infiltrate and HLA-Dr expression in 19 oligodendrogliomas.

We have studied frozen tissue from 19 oligodendrogliomas with a panel of antibodies to lymphocytes and their subsets, macrophages, natural killer cells, and HLA-Dr antigens. Macrophages were detected in moderate numbers in 60%-100% of tumors depending on the antibody used. T lymphocytes were fewer in number than macrophages and were present in 62% of cases. Most of the T lymphocytes were of the CD8 phenotype. CD4 lymphocytes were very few in number and present in only 18%. B cells and natural killer cells were absent from all cases. HLA-Dr antigens were expressed by macrophages in all cases but never on tumor cells. The implications of these findings are that macrophages and, to a lesser extent, CD8 lymphocytes are the predominant cells infiltrating oligodendrogliomas and that they may exert cellular immune functions.

Antibodies, Monoclonal↗

Monocyte/macrophage infiltrate in 41 oligodendrogliomas. Paraffin-wax study.

We have studied wax-embedded tissue from 41 (33 low and 8 high grade) oligodendrogliomas with KP 1, a new monoclonal anti-monocytes/macrophages (M/Ms) antibody. Away from areas of degeneration, M/Ms cells were detected in 63% of low grade and 87% of high grade tumours. The latter had, on average, at least more than twice as many infiltrating M/Ms. It is concluded that our findings may indicate the presence of a host M/Ms immune response and that KP 1 antibody is suitable for the study of such infiltrate, thus lessening (but not obviating) the need for frozen tissue for immunohistological studies.

Antibodies↗

Mononuclear cell infiltrate and HLA-Dr expression in intra- and extradural secondary carcinomas.

Frozen sections from 30 secondary carcinomas (22 intra- and 8 extradural) were reacted with a panel of monoclonal antibodies to macrophages, lymphocytes, NK cells and HLA-Dr invariant chain. A moderate number of macrophages was demonstrated in 91% of tumours. CD 8 and CD 4 lymphocytes were detected in smaller numbers in 68% and 28% of tumours respectively. B lymphocytes were present in only one tumour and NK cells were absent. There was no significant difference between the mononuclear cell infiltrate in the intra- and extradural tumours and in respect to the histological tumour type. HLA-Dr antigen was expressed by macrophages in most cases and by tumour cells in 5/22 (22%) (4 adeno and 1 anaplastic carcinoma; of which one adenocarcinoma was extradural and the remaining intradural). The results may represent evidence for a degree of cellular immune response to secondary carcinomas which is independent of the intra- or extradural location of the tumour.

Antibodies, Monoclonal↗

Oligodendrogliomas: a clinical, histological, immunocytochemical and lectin-binding study.

We have studied 27 oligodendrogliomas with a panel of antibodies (vimentin, GFAP, S-100 protein, myelin basic protein, CAM 5.2) and of lectins (WGA, Con A, PNA, RCA, DBA, SBA) to different glycoproteins. There were 16 well-differentiated tumours, including one gliofibrillary and 11 anaplastic oligodendrogliomas, three of which were gliofibrillary. Four cases showed positivity for vimentin, three of which were anaplastic tumours. Fifteen cases were positive for S-100 protein (nine well-differentiated and six anaplastic tumours) and 13 contained GFAP-positive cells (three well-differentiated and 10 anaplastic tumours). WGA binding was positive in 75% of well-differentiated and 63% of anaplastic oligodendrogliomas, the corresponding figures were 50% and 45% for PNA, 37% and 81% for Con-A and 25% and 54% for RCA. On the basis of the results with lectin binding, we believe that there are changes in the spectrum of tumour cell-associated lectin-like proteins during malignant transformation. Our observations also suggest that the pattern of lectin expression can undergo substantial changes in the course of differentiation.

Adult↗

[Statistical analysis of mediator release from the cyto-neural junction of the posterior canal of the labyrinth isolated from the frog].

The transmitter release mechanism was investigated at the cyto-neural junction of the frog labyrinth posterior canal. Low frequency (less than 100/s) non overlapping EPSPs were intracellularly recorded both at rest and during inhibitory mechanical stimulation of the canal (2-8 deg/s2). Recordings were obtained: in control solution; in the presence of increased external Ca2+ (9 mM); in Ca-free EGTA (5 mM) solution and during electrical activation at 50 Hz of the posterior canal inhibitory efferent system. Individual synaptic potentials were digitized and their peak amplitudes, their time integrals as well as the time intervals between them were evaluated. The time intervals proved to be exponentially distributed, suggesting a random EPSP occurrence. The analytical reconstruction of the EPSP waveform indicated that a gamma- function fitted reasonably well both the single and averaged events. As regards the averaged event, despite the scatter in the values of the gamma-function exponential factor (range 1.1-2.2), in the EPSP time-to-peak (0.6-1.2 ms) and peak amplitude (0.9-2.7 mV) displayed by the units, no significant differences were observed in the same fibre between control and test conditions. Moreover, the event peak amplitude distribution represented by cumulative plots or amplitude histograms was fitted by a lognormal function. The distributions obtained for the same unit in control solution proved to be not significantly different from those successively obtained under test conditions. The unimodal and continuous EPSP distributions, together with the unvarying characteristics of the single events, strongly suggest that the observed potentials are true mEPSPs due to the release of single quanta of transmitter.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗

Immunohistological signposts in central nervous system tumours with neuronal differentiation.

25 neuronal tumours with a panel of antibodies were studied and it was found that vimentin was present in 15 tumours. It was also found in a few cells within rosettes. PGP 9.5 showed a somatic pattern of staining with nuclear and perinuclear positivity in 23. Neurofilament reactivity was found in 14. Retinal S-antigen was detected only in one medulloblastoma, 3/4 pineal tumours and 2/2 retinoblastomas. Reactivity, for synaptophysin was present in 2/5 medulloblastomas, 3/10 neuroblastomas and 2/2 retinoblastomas. GFAP was demonstrated in scattered tumour cells in 4/5 medulloblastomas. Two of these were the only tumours featuring bipolar differentiation whilst it was unipolar in the remainder. The significance of these findings in relation to the ontogeny of these tumours is discussed.

Adolescent↗

Mononuclear cell infiltrate and HLA-Dr expression in 28 pituitary adenomas.

Frozen sections from 28 pituitary adenomas were reached with a panel of monoclonal antibodies to macrophages, lymphocytes and HLA-Dr invariant chain. A low number of macrophages were demonstrated in all tumors, mainly perivascular. CD8 and CD4 lymphocytes were detected in even smaller numbers in 80% and 14% of tumors respectively. B lymphocytes were present in only 1 case. An occasional NK cell was present in 1/13 cases studied. HLA-Dr antigen was expressed by macrophages in all cases and by tumor cells in 2 growth hormone-producing adenomas/19 adenomas. These findings may represent evidence for a low degree of cellular immune response to pituitary adenomas.

Adenoma↗

Epidermal growth factor receptor expression in 72 meningiomas.

The expression of epidermal growth factor receptor (EGF-R) was studied immunohistochemically in 72 meningiomas using two monoclonal antibodies with specificities to protein and carbohydrate components, respectively, of the external domain of the EGF-R. One third of the tumors had cytoplasmic and membrane positivity with the protein-specific antibody but in none were there positive tumor cells with the carbohydrate-specific antibody which recognizes the blood group A antigen. There was no difference in EGF-R expression between typical and aggressive meningiomas. No evidence was found to support previous reports of specific EGF-R immunoreactivity in the vascular endothelial cells of meningiomas. The authors believe this discrepancy to be due to detection of normal blood group A antigen attached to endothelial cells in patients of blood group A or AB. This occurs because many monoclonal anti-EGF-R antibodies are specific for A antigen which is found on the EGF-R of A431 cells but has not been reported on EGF-R elsewhere.

Animals↗