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Biomedical subjects

C Crespi

Publications and source records attributed to C Crespi.

At least 19 recordsLinked to original sources

Changes in autonomic modulation to the heart and intracellular catecholamines. A longitudinal study in differentiated thyroid carcinoma during short-term hypothyroidism and thyroid hormone replacement.

BACKGROUND: The effects of thyroid deprivation on the autonomic modulation to the heart remain controversial. METHODS: In this study in patients followed for thyroid carcinoma, we investigated (1) heart rate variability parameters and the baroreflex gain and (2) intracellular catecholamine levels in circulating lymphocytes during short-term hypothyroidism (phase 1) and after reinstitution of TSH-suppressive thyroid hormone replacement (phase 2). RESULTS: The RR interval value (p < 0.01) and systolic blood pressure (p < 0.05) were higher in phase 1 than in phase 2. The low-frequency/high-frequency (LF/HF) ratio was significantly lower in the hypothyroid state (p < 0.05), with a higher HF component (p < 0.05). After adjusting for mean RR interval in the regression model, the difference between the power of RR interval oscillations calculated in the two states was greater for the LF band (p = 0.005) and it was borderline significant for the HF band (p = 0.052). The baroreflex gain alpha(LF) index was similar in the two phases. The stimulus-induced cellular production of norepinephrine and epinephrine in peripheral blood mononuclear cells was significantly higher in phase 2. CONCLUSION: The neurally-mediated influences on the sinus node and the study of intracellular catecholamine production suggest a reduced sympathoexcitation in hypothyroidism compared with the treatment phase. The early increase in blood pressure observed after thyroid hormone withdrawal is not due to impaired sensitivity of the baroreflex arc.

Autonomic Nervous System↗

Influence of liver fibrosis on hepatic artery Doppler resistance index in chronic hepatitis of viral origin.

BACKGROUND: Hepatic arterial Doppler sonography is increasingly being used in liver diagnostics. The determinants of the elevation of hepatic artery impedance indexes in chronic liver disease, however, have still not been fully clarified. The aim of the present study was to investigate the relationship between histological alterations and liver circulation in chronic hepatitis. METHODS: Hepatic artery resistance index and portal flow velocity were measured using Doppler sonography in 47 patients with chronic hepatitis of viral origin diagnosed at histopathology. The patients were divided into two groups, those with mild and those with severe alterations, in accordance with the various histological parameters of the Knodell scoring system. RESULTS: Hepatic artery resistance index and age were higher in patients with more severe liver fibrosis (respectively 0.638 +/- 0.084 and 39.0 +/- 10.9 (years) in mild fibrosis versus 0.687 +/- 0.060 and 49.4 +/- 14.4 (years) in severe fibrosis; P < 0.05 for both), whereas no difference between the two groups was found for the other histological features (degeneration, inflammation and necrosis), nor for portal flow velocity. CONCLUSIONS: The increase in hepatic artery resistance index appears to be influenced by the extent of fibrous tissue deposition in the liver, determined by chronic inflammation and repair and, secondly, by ageing.

Female↗

Time trends of major coronary risk factors in a northern Italian population (1986-1994). How remarkable are socioeconomic differences in an industrialized low CHD incidence country?

BACKGROUND: The goals are to estimate time trends (1986-1994) of major coronary risk factors in an industrialized low CHD incidence population and to assess education class (EC) differences in risk factor prevalence and in time trends. METHODS: Three population surveys were conducted in 1986-1987, 1989-1990 and 1993- 1994 on independent and two-stage age- and gender-stratified random samples (1906 men and 1941 women) of 35-64 year old residents of Brianza, an affluent region of northern Italy. The protocol for data collection, clinical measurements and biochemical determinations adhered to the WHO MONICA manual and underwent repeated quality control assessments. EC were identified according to gender- and 5-year birth-cohort specific tertiles. RESULTS: In the initial, middle and final surveys 1258, 1259 and 1330 subjects were enrolled, corresponding to participation rates of 70.1%, 70.3% and 74.3%, respectively. Over the 8-year period, in men systolic blood pressure and smoking habits declined, body mass index and serum total cholesterol increased. In women systolic blood pressure showed a constant reduction, total cholesterol and BMI increased and the prevalence of smokers remained stable. Overall inverse associations with EC were found for body mass index, for prevalence of cigarette smokers in men and for systolic blood pressure in women. Decreases in blood pressure were more evident in the lowest EC. Cigarette smoking was on the decline in the higher EC in men. BMI and total cholesterol increased in all EC with the notable exception of the 'low' EC in women. CONCLUSIONS: Favourable changes of the risk factor profile in the low socio-economic classes may have contributed to reduce CHD rates in this population. Specific policies oriented to lowest socio-economic classes are needed to continue to combat the smoking epidemic.

Adult↗

Transient amnesia triggered by acute marijuana intoxication.

We report an unusual case of sudden isolated transient amnesia triggered by acute marijuana use. The memory disorder, apart from the long duration, had the characteristics of a transient global amnesia-like episode. Acute marijuana intoxication can affect memory more globally and severely than previously reported.

Acute Disease↗

Alterations in circulating fatty acids and the compartmentation of selected metabolites in women with breast cancer.

The presence of the tumor in women with breast cancer provokes a profile of biochemical change characterized by hypoglycemia, hyperuremia and high levels of free fatty acids and ketone bodies in plasma. The total circulating levels of amino acids and lactate are slightly higher in patients with breast cancer. Moreover, alterations in the circulating levels of free and total fatty acids are associated with enhanced levels of total free fatty acids and significantly lower levels of esterified arachidonic acid. This profile may indicate a state of moderate catabolic activation in breast cancer patients and may also be associated with a slight mobilization of proteins and fatty acids by some of the peripheral tissues in order to cover the needs of the host and the tumor. However, the alteration in the distribution of different fatty acids (saturated, mono-unsaturated and poly-unsaturated) and the different behaviour of the free and esterified fractions may be the result of a greater release of only specific fatty acids by tumor or other host tissues, rather than a higher release of the whole spectrum of free fatty acids. Thus, it is proposed that some of the alterations may be directly related to localized tumor activity.

3-Hydroxybutyric Acid↗

Results of a pilot study of endoscopic screening of first degree relatives of colorectal cancer patients in Italy.

STUDY OBJECTIVE: Screening recommendations for colorectal cancer include sigmoidoscopy in asymptomatic, average risk persons aged 50 and over and colonoscopy every three to five years in high risk groups. Little is known about the eligible population's compliance with endoscopic screening. This is the first Italian report of an endoscopic screening programme for colorectal cancer patients' relatives. DESIGN: In 1986, a pilot project for colorectal cancer screening by endoscopy in high risk subjects was started in the Desio (Milan, Italy) public health service region. The results obtained after seven years are described. SETTING: The names of 536 inhabitants with colorectal cancer diagnosed between January 1975 and December 1984 and their relatives' addresses were obtained from the Regione Lombardia Health System records and from the municipal registry offices respectively. PARTICIPANTS: From October 1986 to October 1993, 778 first degree relatives aged 20-75 were offered colonoscopy. MAIN RESULTS: After seven years, 233 (29.9%) had undergone endoscopic examination, mostly up to the splenic flexure. Being > 60 in age at the start of the programme negatively affected the participation (p < 0.05). Two cancers were detected and adenomatous polyps were found in another 24 of those screened (frequencies 0.9% and 10.3% respectively). Male gender (p < 0.05), increasing age in males (p < 0.01), and two or more affected relatives in females (p < 0.01) positively affected the frequency of polyps detection. CONCLUSION: These results suggest that about 30% of the eligible population would comply at least with sigmoidoscopic screening. The collaboration of family doctors and more widespread public information about the ability to cure colorectal cancer are necessary for better compliance.

Adenomatous Polyposis Coli↗

[Multiple jejuno-ileal metastasis of malignant schwannoma from the leg. Report of a case presenting anemia symptoms and review of the literature].

A case of jejunal-ileal metastasis from a left leg malignant schwannoma in a 73 year old woman is described. The patient was affected by progressive anemization without signs of bleeding. A colonoscopy performed during hospitalization revealed an ulcerative lesion at the ileo-colonic junction which at histologic examination was suspected for sarcomatous proliferation arising in peripheral nerve tissue. At operation multiple ileal resections of numerous polypoid formations were performed. Histological examination of polypoid masses revealed the presence of malignant proliferation of spindle cells consistent with a malignant schwannoma. Differential diagnoses are discussed with a review of the literature.

Aged↗

Enzymatic determination of carbon (14C)-labeled glycerol in biological samples.

A method for determination of glycerol-specific-radioactivity in biological samples is presented. It is based on the following steps: (a) enzymatic conversion of glycerol to dihydroxyacetone-phosphate, (b) quantitative trapping of dihydroxyacetone-phosphate in SPE amino (NH2) columns, (c) eluation with HCl 0.5 N of dihydroxyacetone-phosphate followed by radioactivity counting and (d) estimation of the radioactivity thus trapped compared with that of enzymatically untreated aliquots of the same samples. No interferences from other 14C-labeled materials tested such as D-glucose, L-alanine, L-glutamine and D-beta-hydroxybutyrate were observed. This inexpensive and high-speed method can be applied in routine multiple estimations of glycerol-specific-radioactivity in biological samples in tracer metabolic studies.

Animals↗

Human CYP2A6 activation of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK): mutational specificity in the gpt gene of AS52 cells.

The tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1- butanone (NNK) is a potential human carcinogen that is known to be metabolized to DNA-reactive intermediates by the cytochromes P450. We have examined the nature of NNK's DNA damaging effects in a mammalian cell system expressing a specific human cytochrome P450 (2A6) and containing a target gene for mutagenesis. Human CYP2A6, which is known to activate NNK to a mutagen, was lipofected via a retroviral vector into the Chinese hamster ovary AS52 cell line, which contains the bacterial gpt gene and can be mutated to 6-thioguanine resistance. AS52 cells expressed negligible CYP2A6-specific coumarin 7-hydroxylase activity (0.7 pmol/mg protein/min), while a CYP2A6 transfected clone (AS52-E8) expressed 30 pmol/mg protein/min. Both cell lines were equally sensitive to the cytotoxic and mutagenic effects of the direct-acting mutagen ethylmethanesulfonate; however, only the AS52-E8 cells exhibited a dose-dependent increase in cytotoxicity and mutant frequency upon treatment with NNK. At the highest NNK dose (1200 micrograms/ml), the mutant frequency in AS52-E8 cells was 14-fold (339 x 10(-6)) greater than the spontaneous frequency of 24 x 10(-6). Ninty-eight mutant clones were isolated following NNK treatment. Based on PCR analysis, 21 clones contained deletions/rearrangements and 77 were putative point mutants. Sequencing potential point mutants showed that 81% contained G:C to A:T transitions. Four of six G:C to A:T hotspots were at the second G of the GGT motif, which is the motif and major mutation found in codon 12 of Ki-ras from NNK-induced lung tumors in strain A mice. Since NNK may be metabolized via different pathways to pyridyloxobutylate or methylate DNA, the data suggest that methylation damage causes the major mutagenic events in AS52-E8 cells when NNK is activated by human CYP2A6.

Amino Acid Sequence↗

Recombinant DNA approaches for the development of metabolic systems used in in vitro toxicology.

In the past few years there has been considerable progress in the development of mammalian cell systems for use in genetic toxicology by the stable transfer of genes/cDNAs coding for drug metabolizing enzymes directly into the target cell. Alternative approaches have also been developed in which mammalian cells are transiently transfected with cDNAs coding for drug-metabolizing enzymes and S9 preparations expressing a single metabolizing enzyme isolated and used for metabolic activation. Progress in these areas is reviewed here and the relative merits of the different approaches are discussed. Work to date has focused primarily on the cytochrome P450 family of enzymes, although other enzyme systems involved in xenobiotic metabolism have been used. The central theme of this review is the transfer of genetic information to improve the metabolic capability of cell systems used in genetic toxicology. However, a basic philosophy of the review is that genetic manipulation of cultured mammalian cells has the potential for developing systems to be used to better understand chemically induced toxicological effects.

Animals↗

[Association of biliary calculosis and portal cavernomatosis].

This paper reports the case of a woman, who underwent surgery because of cholelithiasis, with intraoperative finding of prehepatic portal hypertension from portal vein thrombosis ("portal cavernoma") with healthy liver, later confirmed by angiographic studies. This rare pathologic association carries a higher risk of major operative complications; therefore the Authors agree with the general belief that, for these cases, biliary tract surgery should be as simple and safe as possible. In the case of preoperative diagnosis of biliary disease associated with portal cavernoma, should a surgical approach on the biliary tract be required, we agree on the advisability of performing a shunting procedure before any kind of biliary surgery. In case of variceal bleeding endoscopic sclerotherapy will be the first choice; surgical procedures (shunting) should be seen as a second choice in case of rebleeding after sclerotherapy.

Cholangiography↗

Four year treatment with a long acting somatostatin analogue in a patient with Verner-Morrison syndrome.

The case is described of a woman with a Verner-Morrison syndrome of extreme severity, caused by an occult VIPoma. Administration of SMS 201-995 (Sandoz) (SMS) at the dose of 150 and subsequently of 250 micrograms daily, decreased plasma levels of vasoactive intestinal polypeptide (VIP) from about 500 to 100 pg/ml (highest normal limit 60 pg/ml). This was associated with complete regression of the diarrhea and normalization of serum potassium levels and hence with the return of the patient to a fully normal life. After 36 months of clinical remission, watery diarrhea recurred together with elevation of VIP plasma levels and appearance of liver metastases. Laparotomic exploration led to the removal of a pancreatic VIPoma and its liver secondarisms, which was followed by a second remission. Reappearance of the symptoms and development of new liver metastases 8 months later required reinstitution of SMS therapy, which allowed once again to control the clinical picture. Anterior pituitary function, assessed by dynamic testing, was unaffected by chronic SMS administration with the exception of the stimulated growth hormone secretion that was inhibited. Glucose tolerance and insulin secretion remained normal during treatment. Glucose intolerance ensued after pancreatectomy and was not worsened by reintroduction of SMS. Treatment with SMS may allow long-lasting remission of Verner-Morrison syndrome associated to VIPoma, though it does not arrest the progression of the tumor.

Delayed-Action Preparations↗

[Prolapse of the vaginal vault complicated by ileal evisceration. Possible role of dacron mesh in emergencies. Technical notes].

The prolapse of vaginal vault after hysterectomy is a rather common event, whereas ileal evisceration and intestinal occlusion following a complete rupture of an inverted vaginal vault is extremely rare. The Authors report a case successfully treated using a modified Feldman and Birnbaum colposacropexy. The technique, which takes into account pathophysiologic mechanisms of vaginal prolapse, is described in detail and involves the use of a Dacron mesh.

Aged↗

Transfection of cytochrome P450 cDNAs into mammalian cells used in mutation and transformation assays.

The present work demonstrates that cDNAs coding for cytochrome P450 enzymes can be transfected into mammalian cells and expressed. In the present studies, two different cell systems were used for transfection: 10T1/2 cells which can be used to study initiation and promotion (Diamond, 1984) and AHH-1 cells which can be used to study mutation and clastogenesis (Crespi and Thilly, 1984, Crespi and Penman, 1989). Thus, a diversity of endpoints can be studied in cells which have increased metabolic capability. By increasing the metabolic capability of the target cell, the effects of nongenotoxic as well as genotoxic chemicals, can be examined in the appropriate in vitro systems. For example, the 10T1/2 cells can be treated with a nontransforming dose of an initiator followed by continuous treatment with a second chemical that requires cytochrome P450 specific metabolism to manifest its promoting activity. By this approach, greater insight into the role of chemical metabolism in the promotion process (and presumably other nongenotoxic effects) can be obtained. Additionally, the role of specific cytochrome P450s in the metabolism of different classes of carcinogens/drugs can be elucidated. A major advantage of having the metabolizing enzymes actually present in the target cell is that effects of chemicals can be studied in long-term, low-dose exposure protocols which will eliminate the acute toxic effects which are associated with many current protocols. Thus, more realistic environmental exposure conditions can be achieved by using these in vitro systems containing endogenous metabolism systems.

Animals↗

The mutagenic activity of selected compounds at the TK locus: rodent vs. human cells.

The mutagenic (TFT resistance) and toxic responses of mouse lymphoma (MOLY) L5178Y cells and human lymphoblast (HULY) TK6 cells were compared for 13 chemicals. The mutagenic activities of 8 of the 13 chemicals (62%) examined in the HULY and MOLY assays are in agreement - the results being judged positive in both assays. However, a dramatic difference is observed when the two conditions of metabolic activation are considered separately; the overall concordance of 8/13 has been achieved by combining a 13/13 (100%) agreement in the absence of S9 with a 1/6 (17%) agreement in the presence of S9. In the absence of S9, the concentration ranges, lowest significant doses, and shapes of the concentration-response curves for both toxicity and mutagenicity were similar in spite of the differences in exposure times (4 h for MOLY, 20 for HULY) and expression times (2 days for MOLY, 3 days for HULY). The general agreement observed in the absence of S9 contrasted with the differences manifested in its presence. 6 compounds which were negative in the absence of S9 were tested in both the MOLY and HULY assays in the presence of S9. Of the 6 chemicals, only 1 was positive in both MOLY and HULY under the latter condition; 4 others were positive in MOLY and negative in HULY whereas 1 was positive in HULY and negative in MOLY.

Animals↗

Cytoskeleton organization of normal and neoplastic lymphocytes and lymphoid cell lines of T and B origin.

An anomalous organization of the cytoskeleton has been described in lymphocytes from chronic lymphatic leukaemia and in only few cell lines. We have now studied normal and neoplastic lymphocytes and lymphoid cell lines of both T and B lineage in order to detect morphological differences in the expression of microfilaments and intermediate filaments. Microfilaments appear to be well expressed by all the B cells, whereas a rich network of intermediate filaments is present in T cells and plasma cells. Most prominent changes occur in the latter system, which is almost lacking in cells of B chronic lymphatic and hairy cell leukaemia. Although the significance of the present findings is not yet clear, one might speculate that such alterations account for some of the aberrant functions and peculiar biologic properties of neoplastic lymphocytes.

Actin Cytoskeleton↗

Expression of cytoskeleton components in various Epstein-Barr virus infected cell lines.

It has been shown that viruses can induce alterations in the content and distribution of cytoskeleton structures, particularly actin microfilaments and microtubules. An immunomorphologic study of the cytoskeleton components of various EBV-infected cell lines with expression of different functions of EBV genome has been performed using antibodies to each of its three major components. Intermediate filaments and microtubules were similarly represented in all examined lymphoblastoid cell lines. The distribution of actin microfilaments, on the contrary, differed significantly from cell line to cell line. It is concluded that the morphologic expression of actin might depend on the expression of EBV genome. Furthermore, some of these cell lines might represent a useful substrate for the identification of anticytoskeleton antibodies, mainly anti-actin antibodies, in human sera.

Actins↗

A new method for D-glucaric acid excretion measurement that is suitable for automated instruments.

Urinary excretion of D-glucaric acid (uGA) is an index of type II hepatic microsomal enzyme induction, indirectly revealing possible organic effects of some drugs and environmental pollutants. However, its determination is often cumbersome. We suggest a new, fast microanalytical method for uGA determination in which beta-glucuronidase (BG; EC 3.2.1.31) activity inhibition produced by uGA-derived 1,4-D-glucarolactone is measured. With use of purified BG, the method is suitable for centrifugal analyzers, allowing assay of greater than 100 samples per day. Moreover, the method measures uGA more accurately than other enzymatic methods based on BG inhibition. The within-day CV ranges from 7.9% to 4.6% (uGA 31.55-121.31 mumol/L); the between-day CV ranges from 11.5% to 5.0% (uGA 26.09-124.10 mumol/L). The detection limit is 6.0 mumol/L. The standard curve is linear from 10 to 200 mumol/L. Mean analytical recovery is 100%. Comparison with the method of Simmons et al. (Clin Chim Acta 1974;51:47-51) gave a correlation of r = 0.978, y = 1.40x-2.81. Reference intervals were established in a healthy population sample of 369 people (165 under 14 y), and uGA, expressed in micromoles per gram of creatinine, was higher in women than in girls or in males.

Adolescent↗