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Biomedical subjects

C Boni

Publications and source records attributed to C Boni.

At least 55 records · Page 3Linked to original sources

Linkage of tyrosine hydroxylase to four other markers on the short arm of chromosome 11.

Tyrosine hydroxylase is the rate-limiting enzyme in catecholamine synthesis; the gene has previously been cloned and localised to the short arm of chromosome 11. Because of the interest in tyrosine hydroxylase as a candidate gene for manic-depressive psychosis and other affective disorders, we carried out family studies to determine the linkage of tyrosine hydroxylase with insulin, beta-globin, D11S12 and Harvey-ras 1, members of a linkage group which has previously been localised to 11p. Using DNA from the Centre d'Etude du Polymorphisme Humain (CEPH) and from two large British pedigrees, we show that tyrosine hydroxylase is closely linked to these four loci (z = 7.36, theta = 0.04 for linkage to insulin) and suggest a gene order based on multipoint mapping.

Alleles

Macro serum CK-BB in a woman with severe primary hypothyroidism.

We report the case of a woman with severe hypothyroidism and without concomitant myocardial damage, in whom elevated CK-MB values were measured by radioimmunological and enzymatic methods before and after thyroid replacement therapy. The patient's CK-MB activity was shown to be actually due to an atypical CK band between CK-MM and CK-MB (also termed "macro CK" or "idiopathic serum CK-BB").

Aged

Effects of dilazep on coronary and systemic hemodynamics in humans.

The cardiovascular effects of dilazep, a new antianginal drug, were investigated in 18 patients, who underwent cardiac catheterization and coronary angiography for the evaluation of chest pain. Dilazep, 0.2 mg/kg, was injected intravenously over 1 to 2 minutes. The changes induced by dilazep in coronary tone were assessed by quantitative angiography in four patients, changes in systemic and coronary hemodynamics and blood gases in eight patients, and changes in systemic and pulmonary hemodynamics and blood gases in six. In 6 of the 18 patients the effects on hemoglobin-O2 oxygen binding were also investigated. Following dilazep administration, we observed a marked reduction of coronary resistance (six patients) (0.5 vs 1.0 mm Hg X min X ml-1, p less than 0.01) and of aortic-coronary sinus oxygen difference (seven patients) (4.6 vs 12.3 vol%, p less than 0.01), and a 23% increase in coronary diameter (four patients) (p less than 0.001). Total systemic resistance was also reduced by dilazep (six patients). Conversely, only minimal or insignificant changes were observed in heart rate (14 patients), aortic pressure (14 patients), total pulmonary resistance (six patients), myocardial oxygen consumption (six patients), double product (14 patients), blood gases (seven patients), and hemoglobin-oxygen affinity (six patients). We conclude that dilazep exerts a powerful dilating action on coronary vasculature without appreciable increase of myocardial oxygen consumption and cardiac work simultaneously with a reduction of peripheral resistance.

Adult

Expression of cloned vaccinia virus DNA sequences introduced into animal cells.

Individual cloned HindIII fragments of vaccinia virus DNA were introduced into cells by DNA-mediated gene transfer. The presence of individual fragments in the different transformants was confirmed by Southern blot hybridization analysis. Several of the transformants were found to express viral sequences at various levels. The sizes of the transcripts containing vaccinia virus sequences were highly heterogeneous, with no discrete species of RNA. Positive clones contained vaccinia virus sequences in both the poly(A)+ and poly(A)- RNA fractions, although the prevalence of these sequences was variable in the two fractions. The S1 nuclease map of the 5' end of the transcripts from transformants containing the HindIII-J fragment revealed a unique 5' end, similar to RNA from virus-infected cells. In contrast, analysis of the 3' end of RNAs from these transformants showed a high degree of heterogeneity, which might explain the heterogeneity found in Northern blot patterns. In this report, it is shown for the first time that in cells transformed with vaccinia virus DNA there is proper initiation for, at least, the viral thymidine kinase gene.

Cells, Cultured

Detection of hypothyroid myopathy by measurement of various serum muscle markers--myoglobin, creatine kinase, lactate dehydrogenase and their isoenzymes. Correlations with thyroid hormone levels (free and total) and clinical usefulness.

An accurate and close follow-up of serum levels of thyroid hormones and various muscle markers (myoglobin, creatine kinase and its isoenzymes CK-MB and CK-BB, lactic dehydrogenase, alpha-hydroxybutyric dehydrogenase, etc.) was carried out in 10 hypothyroid patients on replacement therapy. The main muscle markers, creatine kinase and myoglobin, were elevated respectively in 9 and 6 subjects. In 1 male significant CK-MB traces were measured, while in 1 woman significant CK-BB amounts were assayed. Significant correlations between patients' thyroid hormones and the levels of the muscle parameters were found. The rate of normalization of thyroid hormones and muscle markers in relation to replacement therapy was also studied. Myoglobin and creatine kinase have proved to be the best indicators of the hypothyroid myopathy, since they are sensitive for the early detection of muscle involvement due to the metabolic disorder and are closely correlated to the metabolic conditions of patients.

Adolescent

Chemotherapy versus combination of chemotherapy and endocrine therapy in advanced breast cancer. A prospective randomized study.

One hundred-forty-five postmenopausal women with metastatic breast cancer entered a prospective randomized trial comparing treatment A (cyclophosphamide, methotrexate, and 5-fluorouracil; CMF) with treatment B (the same chemotherapy plus tamoxifen; CMF plus T). Patients on treatment A had T added to CMF at the time of progression or relapse (second-line CMF plus T). One hundred thirty-three cases were evaluable. Considering response rate to first-line treatment, CMF plus T appeared to be significantly superior to CMF alone (74 versus 51%, respectively; P less than 0.01). Median time to failure to first-line treatments, considering all patients, was longer in CMF plus T than in CMF arm (48 and 24 weeks, respectively; P = 0.06). Considering patients showing objective remission, median duration of response to CMF was similar to that of CMF plus T (47 and 51 weeks, respectively). Twelve of 39 evaluable women treated with second-line CMF plus T showed objective responses (31%). Median time to failure to treatment procedures scheduled in arm A (CMF leads to CMF + T) was longer than that to treatment in arm B (CMF plus T) (56 and 48 weeks, respectively; P = 0.08). Median survival was longer in patients randomized to treatment A (111 weeks) than in patients randomized to treatment B (78 weeks), but this difference was not statistically significant (P = 0.25). It can be concluded from this study that a combination of endocrine therapy and chemotherapy is significantly more active than chemotherapy alone in inducing an objective remission. This strategy of treatment is advisable in situations urgently requiring a clinical response. However, as a sequence of chemical and endocrine therapy induced a longer time to development of progressive disease and a better survival, sequential therapy is advisable for common clinical use.

Adult

Four methods for glucose assay compared for various glucose concentrations and under different clinical conditions.

Glucose was measured by the ferricyanide, the Beckman glucose oxidase, and the hexokinase procedures in 228 plasma samples taken during standard oral glucose-tolerance tests in 17 normal subjects and in 21 chemical diabetics. The neocuproine method was also used to measure glucose concentration in 156 samples (78 before and 78 after dialysis) collected from six diabetic and uremic patients who were on maintenance hemodialysis. Ferricyanide in all conditions and neocuproine in uremic patients overestimated glucose concentrations over the entire experimental range as compared with either enzymic method. This bias or systematic error of the reducing vs the enzymic procedures, due to nonglucose reducing substances ("saccharoids"), becomes considerably greater when their concentration is increased as in chronic uremia. Also, the inverse relation between glucose concentration and overestimation of glucose by the reducing methods has been detected. With respect to the hexokinase method, a mild but significant underestimate of glucose oxidase readings has been observed for higher glucose concentrations. We find neocuproine to be the most imprecise of these procedures.

Autoanalysis

Decrease in plasma glucose concentration during storage at -20 degrees C.

We measured glucose concentrations with the Beckman Glucose Analyzer, before and after storage at -20 degrees C for various intervals, in 228 plasma samples from oral glucose tolerance tests on 17 normal subjects and 21 patients with impaired carbohydrate tolerance, and also in 82 control samples collected daily, after overnight fast, from seven insulin-dependent diabetics. We found a significantly (p < 0.001) positive relation between storage interval and percentage decrease in glucose concentration. Evidently, the longer plasma is stored, the greater the decrease in glucose.

Blood Glucose

Plasma levels of glucose and lactate after intravenous glipizide administration in some insulin-dependent diabetics. Therapeutic effects of an associated glipizide-insulin treatment.

A study was carried out to evaluate the effectiveness of glipizide in insulin-dependent diabetic patients. An intravenous glipizide (2 mg) test was carried out in 7 patients before and after a period of associated insulin-glipizide treatment (mean daily dose of 80.7 i.v. lente insulin and 14.3 mg glipizide for 9.1 months) to assess the capacity of the sulphonylurea to reduce acutely the plasma glucose and lactate levels. Glipizide did not produce glucose variations in either test but did result in a significant decrease, in the first test only, in mean plasma baseline levels of lactate, which were higher than normal in these patients. There was no reduction in daily insulin requirements after the period of associated glipizide-insulin treatment. It is concluded that, in the dosage used, intravenous glipizide probably has no hypoglycaemic effects in insulin-dependent diabetics. Moreover, it did not prove useful in combination with insulin. However, the reduction in plasma lactate may be related to an acute enhancement of the exogenously administered insulin. This improvement in the insulin effect may be an acute one among the so called "extra-pancreatic" actions which have been demonstrated for glipizide and other sulphonylureas.

Adult

A single human gene encoding multiple tyrosine hydroxylases with different predicted functional characteristics.

Catecholaminergic systems in discrete regions of the brain are thought to be important in affective psychoses, learning and memory, reinforcement and sleep-wake cycle regulation. Tyrosine hydroxylase (TH) is the first enzyme in the pathway of catecholamine synthesis. Its importance is reflected in the diversity of the mechanisms that have been described which control its activity; TH levels vary both during development and as a function of the activity of the nervous system. Recently, we deduced the complete amino-acid sequence of rat TH from a complementary DNA clone encoding a functional enzyme. Here we demonstrate that, in man, TH molecules are encoded by at least three distinct messenger RNAs. The expression of these mRNAs varies in different parts of the nervous system. The sequence differences observed are confined to the 5' termini of the messengers and involve alternative splicing events. This variation has clear functional consequences for each putative form of the enzyme and could represent a novel means of regulating catecholamine levels in normal and pathological neurons.

Adrenal Gland Neoplasms

Soft tissues sarcoma with acute paraneoplastic hepatic dysfunction: case report.

A case of malignant fibrous histiocytoma of soft tissues of the right scapula associated with transitory hepatic dysfunction in the absence of liver metastases is reported. After primary radiation therapy, the patient manifested fever, anemia, thrombocytosis and hepatic dysfunction. All the abnormalities disappeared immediately after complete removal of the tumor. The patient was well, with no evidence of distant metastases, at more than 12 months later. It is concluded that the abnormalities of laboratory data were indirectly induced by the tumor, although the exact mechanism of this paraneoplastic syndrome was not clarified.

Histiocytoma, Benign Fibrous

Neoadjuvant chemotherapy with continuous infusion of cisplatin and fluorouracil in stage II-IV, M0 squamous cell carcinoma of the head and neck.

AIMS AND BACKGROUND: The aim of the study was to assess the activity and the toxicity of cisplatin (DDP) and fluorouracil (FU) administered by continuous infusion as neoadjuvant chemotherapy for patients with stage II-IV, M0 squamous cell carcinoma of the head and neck. METHODS: Thirty previously untreated patients were submitted to chemotherapy with DDP (20 mg/m2) and FU (1000 mg/m2), both in continuous infusion for 5 days, repeated every 21 days, for a maximum of 5 cycles. Following completion of chemotherapy, the patients underwent radiotherapy; in some patients surgery was performed immediately after chemotherapy. All patients were monitored for response, time to failure, survival, treatment-related events and toxicity. RESULTS: All patients were evaluated for response; after chemotherapy the complete response rate was 27% and the partial response rate 33%. Twenty-four patients underwent radiotherapy: the overall response rate was 83% (complete response 79%). After a median follow-up of 34 months, the median survival time was 22 months with a median time to failure of 15 months. Acute vascular accidents were the main and unexpected adverse events, with 2 deaths for pulmonary embolism and 1 for stroke. The response rate to the regimen does not seem to be better than that obtained with the standard combination of cisplatin bolus and fluorouracil continuous infusion. The disadvantage of the regimen is that it causes more discomfort for the patient in that it requires hospitalization. CONCLUSIONS: For this reason, we believe that there are no elements for recommending the schedule as neoadjuvant treatment of patients with squamous cell carcinoma of the head and neck or as an experimental arm in a randomized trial.

Adult

[Impairment of the osteoarticular and musculoligamentous components in bill posters: an example of the thoracic outlet syndrome].

The authors analysed the risks and associated damage in bill posters on the basis of a case history description. Biomechanical analysis of the job revealed in particular the involvement of the musculoligamentous structure of the cervical spine and shoulder, mostly during the actual posting of bills. The authors propose a clinical-functional definition of the pain and paresthetic symptoms of the upper limbs which are frequently encountered in this category of workers.

Adult

The main features of central 5-HT1 receptors.

The 5-HT1 receptor family comprises five different pharmacologic subtypes, designated 5-HT1A, 5-HT1B, 5-HT1C, 5-HT1D, and 5-HT1E, whose common property is to bind 5-HT with nanomolar affinity. Recent investigations with molecular biology approaches led to the cloning and sequencing of 5-HT1A receptors in the rat and in the human, and of the 5-HT1C receptor in the rat. Although the 5-HT1A and 5-HT1C protein binding subunits exhibit the same structure with seven hydrophobic transmembrane domains, an extracellular N terminal and an intracellular C tail, their respective amino-acid sequences are markedly different. Indeed, a higher degree of sequence homology is found between the 5-HT1C and 5-HT2 receptors than between the former and 5-HT1A receptors, suggesting that the 5-HT1C subtype in fact belongs to the 5-HT2 class of central 5-HT receptors. All other 5-HT1 receptor subtypes are negatively coupled to adenylyl cyclase, whereas the 5-HT1C subtype, like 5-HT2 receptors, is positively coupled to phospholipase C. The respective regional distributions and regulatory properties, as well as pending questions regarding the ultrastructural localization, synthesis, mutual interactions, and axonal flow of 5-HT1 receptor subtypes, are also discussed.

Animals