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Biomedical subjects

M Giordano

Publications and source records attributed to M Giordano.

At least 181 records · Page 10Linked to original sources
PubMed1991

Expression of cell cycle related proteins--proliferating cell nuclear antigen (PCNA) and statin--during adaptation and de-adaptation of EUE cells to a hypertonic medium.

EUE cells adapted to grow for long times in a hypertonic medium have a longer cell cycle than those growing in isotonic medium. To elucidate whether this lengthening involves specific cycle phases to differing extents, the expression of two cycle-related protein, PCNA and statin, was studied by dual parameter flow cytometry of indirect immunofluorescence protein labelling and DNA content. In isotonic medium, most cells, in all the cycle phases, were PCNA positive; in contrast, PCNA negative cells and statin positive cells were very few in number and only fell in the G0/1 range of DNA contents. In hypertonic medium, the frequency of PCNA positive cells was lower, and that of statin positive cells higher, than in isotonic medium, particularly in the G0/1 range of DNA contents: this suggests that a G0 block occurs under long-term hypertonic stress. Consistently, dual parameter flow cytometric measurement of BrdUrd immunofluorescence labelling and DNA content showed that fewer cells entered S phase in hypertonic medium and their progression through the S phase was slower; evidence was also found for the occurrence of a G2 block. These kinetics changes were fully reversible in isotonic medium, thus indicating the adaptive nature of the EUE response to hypertonicity.

Adaptation, Physiological↗
PubMed1991

Melatonin-induced enhancement of antibody-dependent cellular cytotoxicity.

Antibody-dependent cellular cytotoxicity (ADCC) is a lytic mechanism in which a specific antibody acts cooperatively with leukocytic effector cells to induce target cell lysis. In this paper, the effect of exogenous melatonin on ADCC was examined. It was found that two evening intravenous injections of melatonin (1 mg/kg b.w.) was sufficient to enhance the capacity of splenocytes to mediate ADCC. This augmented activity returned to normal levels by day 6. Moreover, the opioid antagonist, naloxone, was unable to inhibit the ADCC enhancement, suggesting that melatonin did not operate through a naloxone-sensitive opiatergic mechanism. These results further support the modulatory action of melatonin on immune responses.

Animals↗
PubMed1991

Elevated dietary protein intake impairs the renal hemodynamic response to hyperaminoacidemia in patients with primary glomerular diseases.

We have evaluated the renal hemodynamic response to a mixed amino acid infusion in 7 control subjects and in 8 patients with primary glomerulonephritis (GN). In order to evaluate the role of dietary protein intake in this response, GN patients were maintained for 3 weeks on two separate dietary regimens providing 130 +/- 5 g of protein/day (study 1) and 60 +/- 3 g of protein/day (study 2), respectively. Normal subjects were studied while consuming a free diet. In GN patients, following the reduction in dietary protein intake basal RPF and GFR decreased from 589 +/- 109 to 422 +/- 81 ml/1.73 m2/min (p less than 0.01, vs. study 1) and from 75 +/- 7 to 70 +/- 8 ml/1.73 m2/min (p = NS). Filtration fraction rose from 0.14 +/- 0.02 to 0.19 +/- 0.03 (p less than 0.05). In study 1, during amino acid infusion GFR and RPF did not change significantly from baseline (75 +/- 7 vs. 66 +/- 8 ml/1.73 m2/min at 180 min and 589 +/- 109 vs. 567 +/- 102 ml/1.73 m2/min, respectively). These results are at variance with data obtained in normal controls in whom both GFR and RPF rose significantly following hyperaminoacidemia. In contrast, when dietary protein intake was reduced, a normal renal hemodynamic response to amino acid infusion was restored (GFR went from 70 +/- 8 to 90 +/- 18 ml/1.73 m2/min and RPF from 422 +/- 81 to 517 +/- 90 ml/1.73 m2/min, both p less than 0.05 vs. basal), both absolute and percentage increases were similar to what was observed in controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Cell proliferation of human leukemia and solid tumors studied with in vivo bromodeoxyuridine and flow cytometry.

Bromodeoxyuridine (BUDR) is a thymidine analog that is incorporated into the DNA of proliferating cells. Because the dose of BUDR that is needed to label cells is not toxic, cell labeling can be accomplished in vivo by infusing the substance into patients. A monoclonal antibody against BUDR is then used to identify BUDR-labeled cells. The same cell population can also be stained for DNA content with propidium iodide (PI). Using bivariate flow cytometry (FCM) for measurements, both the percentage of BUDR-labeled cells and their total DNA content can be evaluated. This technique allows one to obtain the labeling index (LI) and the DNA synthesis time (TS). The potential doubling time (Tpot) and the fractional turnover rate (FTR) can be mathematically derived. During a 15-month period, in vivo BUDR infusion to study cell kinetics was used in 112 consecutive patients with various types of malignant tumors: acute leukemia (50), gastric cancer (42), and brain gliomas (20). The procedure took 6 to 9 h to complete and there was no immediate toxicity from BUDR administration. Successful LI and TS determinations were obtained in 89 (80%) and in 80 (72%) of the 112 patients, respectively. Proliferative activity in 34 patients with acute nonlymphoblastic leukemias who were uniformly treated for remission induction and maintenance was measured from Tpot and FTR. It was greater in responsive than in nonresponsive patients, and in those who experienced remission for over 8 months than in those who had a shorter remission. Proliferative activity was also greater in patients with advanced gastric cancers than in those with more limited disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1990

The effects of cocaine on multivariate locomotor behavior and defecation.

The present study utilized a multifactorial open-field analysis (Digiscan activity) to assess behavioral changes induced by various doses of cocaine known to stimulate locomotion. The measures that were implemented included ambulation, rearing, stereotypic behavior, rotational movements and changes in defecation levels. Thirty-two male Sprague-Dawley rats were habituated to Digiscan-16 Animal Activity Monitors (Omnitech Electronics, Columbus, OH) before being injected with 0.0, 10, 20 or 30 mg/kg cocaine. Rats were kept on a reversed light/dark schedule and tested in the middle of the dark cycle. It was found that cocaine consistently increased activity measures; most prominently affecting the rotational and ambulatory indices. Interestingly, this 'activity print' appeared to be dose-dependent and specific to cocaine. Open-field defecation levels were compared to home-cage levels as an additional behavioral correlate. Defecation decreased under all doses of cocaine as compared to control levels (saline injection). This result is attributed to cocaine's weakly sympathomimetic effect.

Animals↗
PubMed1990

Behavioral effects of neural transplants into the intact striatum.

The behavioral effects of fetal brain tissue and adrenal medulla transplants into the intact striatum of rats were investigated. Following a bilateral injection of 1.5, 3 or 6 microliters of fetal striatal tissue, a volume-related weight loss was found in all transplanted groups, including the SHAM group, during the first 7 days after the surgery. Rearing behavior was changed in a transplant volume-related manner. Histological analysis suggested that the locomotor effects of transplants into the intact striatum are related to the volume of the transplants. Following bilateral transplantation of fetal cortex (CTX), substantia nigra (SN), striatum (STR), or adrenal medulla (AM) into the striatum, the different behavioral deficits were observed among these transplant groups. The SN group showed a decrease in spontaneous locomotion, significantly increased rearing activity in response to administration of amphetamine, reduction of food intake and water intake and a reduction in body weight. The CTX and AM groups showed a marked increase in spontaneous rearing activities. Hyporesponsiveness to the administration of apomorphine (1 mg/kg) and amphetamine (1 mg/kg) was evident in the CTX, STR, AM groups and SHAM groups. In contrast, the haloperidol-induced catalepsy scores of the CTX, STR, SN and AM were significantly higher than those of a normal control group. In addition, the CTX group showed a deficit in the delayed reward alternation test. These results indicated that the behavioral deficits produced by transplants into normal striatum may be related to both mechanical destruction due to transplant expansion and specific neurochemical interactions of each tissue type between the host and the transplant. Therefore, potential negative consequences of neural transplantation therapy should be considered as well as the beneficial effects.

Animals↗
PubMed1990

Expression of p53 protein during the cell cycle measured by flow cytometry in human leukemia.

The nuclear protein p53 has been reported to be associated with cell transformation and/or proliferation so that the study of p53 expression in human malignancy has potentially important clinical implications. We have analyzed the p53 expression in mitogen-stimulated and nonstimulated human lymphocytes, in several human leukemia cell lines (Molt-4, Raji, Daudi, HL-60, KG-1, K562 and U937) and in fresh bone marrow (BM) cells. Simultaneous differential staining of p53 (identified by a FITC-labeled monoclonal antibody) versus DNA (stained with propidium iodide, PI), followed by bivariate analysis with flow cytometry (FCM) made it possible to evaluate p53 expression with respect to cell position during the cell cycle. The data show that in stimulated lymphocytes p53 is progressively accumulated during the G1, S and G2-phases, while in non-stimulated conditions most cells are remaining in G0/G1 and express p53 to a lesser degree. This suggests that expression of p53 is more correlated with cell growth than with entrance into (or progression through particular phases of) the cell cycle. Cells from acute lymphoblastic leukemia (ALL) and Burkitt's lymphoma cell lines express elevated levels of p53, while all examined human acute myeloid leukemia cell lines synthesize negligible p53 protein. Understanding the variations in p53 expression in different types of human leukemia may provide some insight into the biologic roles of p53 in normal and malignant cells.

Bone Marrow↗
PubMed1990

MK801 prevents quinolinic acid-induced behavioral deficits and neurotoxicity in the striatum.

Bilateral intrastriatal injections of quinolinic acid (QA) (180 nmoles) induced weight loss and neurologic and behavioral deficits including convulsions, decreased catalepsy response to haloperidol, increased nocturnal locomotor activity, and abnormal feeding behavior in adult male Sprague-Dawley rats. Pretreatment with the noncompetitive N-methyl-D-aspartate (NMDA) antagonist, MK801 (4 mg/kg IP) 30 min prior to stereotaxic surgery prevented the appearance of all QA-induced behavioral abnormalities and prevented weight loss. Twelve weeks after surgery the QA-lesioned animals recovered to sham levels on feeding behavior and nocturnal locomotor activity, but showed persistent reductions in haloperidol-induced catalepsy. Histological examination of the QA-lesioned brains showed extensive lesions of the dorsolateral striatum and frontoparietal cortex. MK801 pretreatment protected against these lesions. These results confirm that MK801 treatment prevents the appearance of neuropathological damage after QA neurotoxicity, and further show that neuronal protection with MK801 is correlated with the absence of QA-induced behavioral deficits.

Brain↗
PubMed1990

Tyrosine hydroxylase-positive fibers and neurons in transplanted striatal tissue in rats with quinolinic acid lesions of the striatum.

Using the quinolinic acid (QA) animal model of Huntington's disease (HD) the dopaminergic afferent input to intrastriatal striatal grafts was examined. After bilateral striatal lesions with QA (15 nmol), 4 microliters of fetal (E17) striatal tissue were delivered into the lesioned striata. Twenty-eight weeks posttransplantation the tissue was processed for TH immunocytochemistry and cresyl violet staining. In addition fetal intact brains (E17) were also processed for TH immunocytochemistry and cresyl violet staining. Viable striatal grafts were located within the host striatum and in some cases within the lateral ventricles. TH-positive fibers were present within the graft and also groups of TH-positive cell bodies were seen in some of the grafts. TH immunocytochemistry on E17 fetuses revealed several groups of TH-positive neurons one of which was placed immediately ventral to the developing striatal ridge. The origin of TH-positive innervation within the graft is discussed.

Afferent Pathways↗
PubMed1990

Neural grafts and pharmacological intervention in a model of Huntington's disease.

Using the excitotoxic animal model of Huntington's disease, two experimental treatments were evaluated. The first experiment explored the effect of MK801 (a systemically active anticonvulsant, and noncompetitive NMDA antagonist) pretreatment on quinolinic acid (QA)-induced striatal degeneration and behavioral deficits. MK801 prevented QA-induced neuropathological changes in the striatum and the anatomical protection was correlated with the absence of deficits in the cataleptic response to haloperidol. The second experiment tested the ability of three types of fetal grafts to reverse behavioral deficits induced by kainic acid (KA) lesion. Fetal (E15-16) striatal, cortical and tectal grafts were delivered into the KA-lesioned striatum one week or one month after lesion. Animals in this experiment were evaluated on a motor coordination task, haloperidol-induced catalepsy and amphetamine-induced locomotor activity. Striatal grafts attenuated the deficits induced by KA in all of the tasks observed, and no effect of time of grafting was detected. Tectal grafts had a partial beneficial effect, attenuating the decrease in the cataleptic response to haloperidol observed after KA lesions. No effect of time of grafting was detected for these grafts. In contrast, a clear effect of time of grafting was detected for the cortical grafts. Early cortical grafts reversed the exaggerated response to amphetamine observed after KA lesions whereas late cortical grafts resulted in sham-like scores on the catalepsy test. Histochemical analysis showed that most of the grafts survived, had acetylcholinesterase (AChE) positive fibers and cell bodies, and were metabolically active as indicated by cytochrome oxidase (CO) positive staining. It is suggested that striatal grafts may have restored to some extent the striatal GABAergic control over output structures, and that trophic factors play a role in behavioral recovery as is evident from the beneficial effects of the tectal grafts. Although the mechanisms underlying the differential effects observed after early or late cortical grafts are unknown, the interaction between the cellular components and trophic factors present in the cortical grafts and the condition of the lesioned host at the time of grafting may yield a host-graft complex with a unique profile.

Acetylcholinesterase↗
PubMed1990

Ras oncogene expression and DNA content in plasma cell dyscrasias: a flow cytofluorimetric study.

Using bivariate flow cytofluorometry, we have determined the nuclear DNA distribution and the expression of the p21 protein (coded by the Ha-ras oncogene) in the bone marrow (BM) cells of five solid tumour patients having histologically normal BM and in those of 57 patients with plasma cell dyscrasia (28 with monoclonal gammopathies of undertermined significance, MGUS, and 29 with multiple myeloma, MM). All normal and MGUS and 21/29 (72.4%) MM BM had diploid modal DNA content and 8/29 (27.6%) MM BM had both diploid and hyperdiploid cell populations. In normal and MGUS BM, the level of the p21 oncoprotein was low and uniform in all G0/G1, S and G2 cells (median fluorescence values in arbitrary units were 6.1 and 7.5, respectively). The level of p21 was increased both in different aliquots of G0/G1 cells and in the S and G2 cells in diploid MM (median value for G0/G1 cells was 20), and especially in MM with hyperdiploid clones (median value for hyperdiploid cells was 40.5, P less than 0.005 with respect to normal and MGUS BM and less than 0.005 with respect to diploid MM BM). The p21 expression was greater in patients with advanced (stage III) than in earlier MM (stages I + II) (P less than 0.005), and it was directly related to the BMPC infiltration (r = 0.7; P less than 0.005). Since p21 expression is greater in MM than in both normal and MGUS BM, Ha-ras could be involved in the malignant plasma cell transformation that distinguishes MM from MGUS.

Bone Marrow↗
PubMed1990

Granulocyte-macrophage and macrophage colony-stimulating factors activate intramacrophage killing of Leishmania mexicana amazonensis.

Leishmania organisms are important pathogens, causing diseases worldwide. Standard therapies are often toxic and are not always effective. The effect of recombinant human granulocyte-macrophage and macrophage colony-stimulating factors (GM-CSF and M-CSF) on intramacrophage survival of Leishmania mexicana amazonensis (Lma) were compared with those of interferon-gamma (IFN-gamma). Macrophages previously infected with Lma were treated with or without GM-CSF and M-CSF. Compared with no cytokine treatment, treatment with GM-CSF (0.1-100 ng/ml) or M-CSF (1:3.5 X 10(6) - 1:3.5 X 10(3) dilutions) caused a significant dose-dependent reduction in intracellular parasites, 427 +/- 20 (mean +/- SE) Lma/100 macrophages. GM-CSF or M-CSF in combination with IFN-gamma resulted in more effective inhibition of intracellular parasites. Thus, the cytostatic activity appears to require interaction between cytokines, macrophages, and amastigotes. These cytokines are potential therapeutic agents for visceral leishmaniasis.

Animals↗
PubMed1990

Isolation of cDNA fragments hybridizing to rat brain-specific mRNAs.

A cDNA minilibrary in pUC18 has been generated from 3-month-old rat brains. Two hundred clones were randomly selected and sequenced. Comparison with a nucleic acid and protein data bank revealed a number of cDNA fragments not homologous to any published sequence. Northern blot analyses of some of these clones yielded 5 brain-specific cDNA fragments. The full-length cDNA for one of these clones has been isolated and completely sequenced. It corresponds to an mRNA of about 1,500 nucleotides, which is present in brain and, to a lesser extent, in heart and skeletal muscle. Its expression is developmentally regulated in the rat brain from 14-day embryos to 3-month-old adults. A very recent comparison with the EMBL nucleotide sequence data bank showed that this mRNA codes for a brain-specific snRNP-associated protein.

Aging↗
PubMed1990

Immunocytochemical evaluation of proliferative activity in human brain tumours.

The immunocytochemical expression of the antigen reacting with the monoclonal antibody Ki-67 (Ki-67 positivity) was investigated in 50 imprint preparations from human brain tumours. Data were related to tumour proliferative activity, as determined from in vivo bromodeoxyuridine (BrdU) incorporation (BrdU-labelling index, BrdU-LI) and histology. The percentage of Ki-67-positive cells was greater than the corresponding BrdU-LI value in all tumours, and the differences in Ki-67 positivity among tumour subtypes paralleled the BrdU-LI differences. Both the BrdU-LI and the percentage of Ki-67 positive cells were significantly greater (P less than 0.005) in the group of clinically aggressive adult tumours, histologically identified as anaplastic astrocytomas and glioblastomas, than in the less aggressive ones (oligodendroglioma, meningiomas, schwannomas, pituitary adenomas, dermoid cyst) and in the cerebral metastatic localizations. These data suggest that Ki-67 positivity, which is easily evaluated with immunocytochemistry, is related to the proliferative activity of brain tumours and that this parameter is endowed with clinical significance.

Antibodies, Monoclonal↗
PubMed1990

[Glossopharyngeal neuralgia].

Glossopharyngeal neuralgia, such less common than trigeminal neuralgia, is characterized by paroxysm of unilateral pain with sudden onset radiating from the oropharynx and base of the tongue, to the ear. Often precipitated by swallowing the glossopharyngeal neuralgia is occasionally accompanied by bradycardia or syncope. Conservative treatment consists of anticonvulsant drugs. Surgical treatment consists of section of the rootlets of the ninth and, in part, tenth cranial nerves. In some selected patients microvascular decompression without section of rootlets is also been made.

Glossopharyngeal Nerve↗