Aromatic L-amino acid decarboxylase-immunohistochemistry in the cat lower brainstem and midbrain

By indirect immunohistochemistry, the present study examined the distribution of neuronal structures in the cat medulla oblongata, pons, and midbrain, showing immunoreactivity to aromatic L-amino acid decarboxylase (AADC), which catalyzes the conversion of L-3, 4-dihydroxyphenylalanine (L-DOPA) to dopamine, and 5-hydroxytryptophan to serotonin (5HT). With simultaneous and serial double immunostaining techniques, immunoreactivity to this enzyme was demonstrated in most of the catecholaminergic and serotonergic neurons. We could also demonstrate AADC-IR cell bodies that do not contain tyrosine hydroxylase (TH-) or 5HT-immunoreactivity (called "D-type cells") outside such monoaminergic cell systems. At the medullo-spinal junction, very small D-type cells were found within and beneath the ependymal layer of the 10th area of Rexed surrounding the central canal. D-type cells were localized in the caudal reticular formation, nucleus of the solitary tract, a dorsal aspect of the lateral parabrachial nucleus, and pretectal areas as have been reported in the rat. Furthermore, the present study describes, in the cat brainstem, new additional D-type cell groups that have not been reported in the rat. Dense or loose clusters of D-type cells were localized in the external edge of the laminar trigeminal nucleus, dorsal motor nucleus of the vagus, external cuneate nucleus, nucleus praepositus hypoglossi, central, pontine, and periaqueductal gray, superficial layer of the superior colliculus, and area medial to the retroflexus. D-type cells were loosely clustered in the lateral part of the central tegmental field dorsal to the substantia nigra, extending dorsally in the medial division of the posterior complex of the thalamus and medial side of the brachium of the inferior colliculus. They extended farther rostrodorsally along the medial side of the nucleus limitans and joined with the pretectal cell group. Almost all these cells were very small and ovoid to round with 1-2 short processes with the exception of dorsal motor vagal cells. AADC-IR axons were clearly identified in the vagal efferent nerves, longitudinal medullary pathway, dorsal tegmental bundle rostral to the locus coeruleus. Serotonergic axons were identified not only in the central tegmentum field and lateral side of the central superior nucleus, but also in the ventral surface of the medulla oblongata. We describe principal densely stained fiber plexuses in the cat brainstem. The findings of the present study provide a morphological basis for neurons that decarboxylate endogenous and exogenous L-DOPA, 5HTP, and other aromatic L-amino acids.     

A phase I study of SR-4554 via intravenous administration for noninvasive investigation of tumor hypoxia by magnetic resonance spectroscopy in patients with malignancy.

PURPOSE: To perform a Phase I study of SR-4554, a fluorinated 2-nitroimidazole noninvasive probe of tumor hypoxia detected by (19)F magnetic resonance spectroscopy (MRS). EXPERIMENTAL DESIGN: SR-4554 administration, on days 1 and 8, was followed by plasma sampling for pharmacokinetic studies and by three MRS studies performed over 24 h on days 8 and 9. Unlocalized MR spectra were acquired from tumor (10- or 16-cm dual resonant 1H/19F surface coil; 1.5 T Siemens Vision MR system; 2048 transients acquired over 34 min; 1.28-ms adiabatic pulse; repetition time, 1 s). Plasma drug concentrations were measured with a validated high-performance liquid chromatography method. Noncompartmental pharmacokinetic analysis was performed. RESULTS: Eight patients underwent pharmacokinetic studies, receiving doses of SR-4554 of 400-1600 mg/m(2). Peak plasma concentrations increased linearly with the SR-4554 dose (r(2) = 0.80; P = 0.0002). The plasma elimination half-life was relatively short (mean +/- SD, 3.28 +/- 0.59 h), and plasma clearance was quite rapid (mean +/- SD, 12.8 +/- 3.3 liters/h). Urinary recovery was generally high. SR-4554 was well tolerated. A single patient experienced dose-limiting toxicity (nausea and vomiting) at 1600 mg/m(2). The maximum tolerated dose was 1400 mg/m(2). SR-4554 was detected spectroscopically in tumors immediately after infusion at doses of 400-1600 mg/m(2). At the highest dose (1600 mg/m(2)), SR-4554 was detectable in tumor at 8 h, but not at 27 h. CONCLUSIONS: SR-4554 has plasma pharmacokinetic and toxicity profiles suitable for use as a hypoxia probe. It can be detected in tumors by unlocalized MRS. Additional clinical studies are warranted.     

Abdominal Pain Severity Is Mainly Associated with Bloating Severity in Patients with Functional Bowel Disorders and Functional Abdominal Pain

Digestive Diseases and Sciences - Abdominal pain is a cardinal sign of functional bowel disorders (FBD), in favor of irritable bowel syndrome (IBS). However, the determinants of abdominal pain...     

Mutations in JAGGED1 gene are predominantly sporadic in Alagille syndrome

BACKGROUNDS & AIMS: Mutations in the JAGGED1 gene are responsible for the Alagille syndrome, an autosomal dominant disorder characterized by neonatal jaundice, intrahepatic cholestasis, and developmental disorders affecting the liver, heart, vertebrae, eyes, and face. We screened a large group of patients for mutations in JAGGED1 and studied transmission of the mutations. METHODS: The coding sequence of the JAGGED1 gene was searched by single-strand conformation polymorphism and sequence analysis for mutations in 109 unrelated patients with the Alagille syndrome and their family if available. RESULTS: Sixty-nine patients (63%) had intragenic mutations, including 14 nonsense mutations, 31 frameshifts, 11 splice site mutations, and 13 missense mutations. We identified 59 different types of mutation of which 54 were previously undescribed; 8 were observed more than once. Mutations were de novo in 40 of 57 probands. CONCLUSIONS: Most of the observed mutations other than the missense mutations in JAGGED1 are expected to give rise to truncated and unanchored proteins. All mutations mapped to the extracellular domain of the protein, and there appeared to be regional hot spots, although no clustering was observed. Thus, the sequencing of 7 exons of JAGGED1 would detect 51% of the mutations. Transmission analysis showed a high frequency of sporadic cases (70%).     

Inflammatory pseudotumor of lymph node

INTRODUCTION: Inflammatory pseudotumor of lymph node is a rare case in the etiology of fever of unknown origin. OBSERVATION: We report the observation of a woman, aged 40, hospitalized with intermittent fever revealing under-diaphragm adenopathy related to inflammatory pseudotumor of lymph node. CONCLUSION: Inflammatory pseudotumor of lymph node is a rare pathology whose nosological definition is unclear. It should probably be considered as belonging to a category different from the inflammatory pseudotumor of other organs. The diagnosis presents itself in case of isolated adenopathy or prolonged fever and is based on an anatomopathology that essentially calls to mind a lymphoma. The evolution of the condition is shown to be favorable : it can lead to a spontaneous remission, or call for a non-steroid anti-inflammatory treatment, or a steroid therapy.     

Effect of estrogen plasma binding on sexual differentiation of the rat fetus.

alpha-Fetoprotein, the estradiol-binding plasma protein (EBP), binds estradiol but not R 2858 (11beta-methoxy-17-ethynyl-estradiol) specifically. R 2858 interferes more markedly than estradiol with the sexual differentiation of the male rat fetus following treatment of the mother during the final stages of gestation. Moreover, its tissular uptake is higher. These facts suggest that alpha-fetoprotein protects the fetus from the high circulating hormone concentrations present in the pregnant mother. The hormone, once transferred to the fetus, is retained in its vascular bed by EBP.     

Analysis of segmental kinetics of the left ventricle after intravenous administration of urokinase in the acute phase of myocardial infarction

From 1982 to 1984 included, 31 patients under 70 years of age were admitted during the first three hours of a primary myocardial infarction (MI) and are the subject of a randomized prospective study. 16 patients are treated with 5,000 U of heparin given in intravenous bolus, followed with 150,000 IU of urokinase (UK) in intravenous bolus, then 12,000 IU of UK/min for 90 min or a total dose of 1,230,000 IU. 15 patients are treated with heparin alone (intravenous bolus of 5,000 U). Repeated titrations of creatine phosphokinase (CPK) and the coagulation parameters are performed during the first 24 hours. A coronary angiography with ventriculography (RAO 30 degrees) is performed on the 1st day (D1) and the 3rd week (W3). Study of the left ventricular kinetics (LV) is carried out according to the Stanford method. At D1, the rate of coronary patency is 56 p cent (n = 9) in the UK (A) group and 53 p. cent (n = 8) in the control group B (heparin alone). The percentage of late re-thrombosis is 0 p. cent in group A and 12.5 p. cent in group B (heparin alone). 1 patient died in each group. The CPK peak is less high in case of coronary patency in group A than in case of thrombosis (1,444 +/- 413 vs 1,710 +/- 120 U -heparin alone) and occurs earlier (16 +/- 2 h vs 21 +/- 1 h). In group A a significant decrease of fibrinogen (p. 0.01) as well as plasminogen and alpha-2-antiplasmins (p less than 0.001), is noted. No severe haemorrhagic complications nor sustained rhythm disorders are noted.(ABSTRACT TRUNCATED AT 250 WORDS)