Fluid and Protein Secretion by the Submandibular Glands of Weanling Rats in Response to Cholinergic and Peptidergic Agonists at Various Doses

Fluid and protein secretion by the submandibular glands of 25-day-old rats were examined and compared in response to three cholinergic and four peptidergic sialogogues at various doses. All cholinergic and peptidergic agonists used were potent sialogogues for the submandibular glands of the weanling rats over the wide range of doses used. The cholinergic agonists, bethanechol and methacholine and the peptidergic agonists, substance P, substance P^Tyr8 and eledoisin-related peptide used intravenously, acted similarly to each other on the submandibular glands of the rats, late in the natural weaning period, but carbachol and physalaemin had slightly different effects. Of the peptidergic agonists, physalaemin was the most potent sialogogue among four tachykinins tested at the low dose. The types of protein secreted by the submandibular glands of the weanling rats in response to all sialogogues used here were typical of the β-type. These results indicate that all agonists used could mainly stimulate the acinar cells of the submandibular glands of the weanling rats which have already fully developed functionally at this time.     

Role of vagotony in sinus node dysfunction in children with symptomatic congenital long QT syndrome

The present study examined chronotropic dysfunction and the role of vagotony in congenital long QT syndrome, sinus node function and the effects of parasympathetic blockade. Six patients with congenital long QT syndrome were studied. The four males and two females, aged 1–15 years, had episodes of syncope and malignant ventricular arrhythmias. Congenital long QT syndrome was defined as a corrected QT interval greater than 0.45 s, T wave alternans and the age at diagnosis. The sinus heart rate measured from a 24 h electrocardiograph was abnormally low (< 50 min) in three patients (1, 4 and 5 years old) and did not increase sufficiently with the administration of atropine in five of the six patients with congenital long QT syndrome. From intracardiac electrophysiological studies, the corrected sinus node recovery time was prolonged in three patients and the total sinoatrial conduction time was prolonged in two patients. In most patients who had an abnormally long sinoatrial conduction time and corrected sinus node recovery time, these values returned to normal following atropine administration. In one patient, the corrected sinus node recovery time was prolonged paradoxically by atropine. Sinus node dysfunction in congenital long QT syndrome was affected by vagotony associated with a right sympathetic nerve system abnormality.     

Hemophagocytic lymphohistiocytosis in a human immunodeficiency virus-positive homosexual high school student

The spread of human immunodeficiency virus (HIV) infection has exploded over the past two decades and such infections in young people are no longer uncommon. However, the major infection route of pediatric patients remains vertical transmission, and sexual, especially homosexual transmission, is highly unusual. We herein describe the case of a 17-year-old boy who developed hemophagocytic lymphohistiocytosis (HLH). Although HLH was remitted soon with dexamethasone therapy, an HIV infection caused by homosexual transmission was detected.     

Solution structure of the phosphorylated sites of ribosomal protein S6 by 1H NMR spectroscopy

An increase in the rate of protein synthesis is found to be accompanied by phosphorylation of the 40S ribosomal protein S6. Treatment of S6 by cyanogen bromide produced three fragments, and one of the fragments of S6, which is a C-terminal portion of S6 (M_r? 4000), contains all phosphorylation sites of S6. The C-terminal fragment of S6 contains seven serines. S6 kinase phosphorylates S6 specifically, i.e. five serines in the C-terminal of S6 are phosphorylated. The three-dimensional structure of S6 peptide was studied in 50% trifluoroethanol/50% H₂O solution by ¹H NMR with combined use of distance geometry and restrained molecular dynamics calculations. NMR results indicated that it takes an α-helix between Glu5 and Arg21 and a distorted helical structure for the following three residues, but no rigid structure was present from Ser25 through the C-terminus and for the N-terminal region (Lys1-Lys4). The specificity of the phosphorylation of the peptide is discussed from a structural aspect. © Munksgaard 1996.     

Solution structure of a human calcitonin analog elucidated by NMR and distance geometry calculations

Three-dimensional structure of a human calcitonin analog (abbreviated as hCTa) in which the amino acids of the wild type are replaced at positions 12, 16 and 19 by leucine residues and further at position 22 by a tyrosine residue was studied in TFE solution by ¹H-NMR and distance geometry calculations. This analog has a 15-20 times activity as compared with the wild type. The amino acid replacements resulted in formation of an amphiphilic α-helix in the region between the residues 4-20. The overall three-dimensional structure is similar to that of the wild type. The conformational feature of hCTa with a hydrophobic face composed with a Met and four Leu residues may be related to its higher hypocalcemic potency.     

Heart Rate Turbulence as a Predictor of Cardiac Mortality and Arrhythmic Events in Patients with Dilated Cardiomyopathy: A Prospective Study

Background: Few studies have described the clinical usefulness of heart rate turbulence (HRT), an autonomic predictor of mortality, in stratifying patients with dilated cardiomyopathy (DCM) at risk of cardiac mortality and arrhythmic events. We prospectively assessed the utility of HRT for risk stratification in patients with ischemic or nonischemic DCM.
Methods: We enrolled 375 consecutive patients with DCM including ischemic (n = 241) and nonischemic causes (n = 134). HRT was measured using an algorithm based on routine 24-hour Holter electrocardiograms, assessing 2 parameters: turbulence onset (TO) and turbulence slope (TS). HRT was considered positive when both TO was ≥0% and TS was ≤ 2.5 ms/R-R interval. The primary endpoint was defined as cardiac mortality and the secondary endpoint as occurrence of hemodynamically stable sustained ventricular tachyarrhythmias.
Results: Of patients enrolled, 83 patients (22.1%) were not utilized for HRT assessment because there were too few ventricular premature beats, or for other reasons. Eighty-one of 292 patients (27.7%) were HRT-positive. During follow-up of 445 ± 216 days, 30 patients (10.3%) reached the primary endpoint and 17 patients, the secondary endpoint. The hazard ratio (HR) of patients with an HRT-positive outcome was 6.4 (95%CI, 3.0–14.1; P < 0.0001) for the primary endpoint and 5.1 (95%CI, 2.8–9.3; P < 0.0001) for combined endpoints. On subanalysis, HRT positivity was significantly associated in both the ischemic and nonischemic DCM patients with both the primary endpoint (HR = 4.9, P = 0.0006 and HR = 12.3, P = 0.002, respectively) and with combined endpoints.
Conclusions: HRT is a powerful risk stratification marker for cardiac mortality and arrhythmic events in patients with DCM whether ischemia is present or not.     

Left and right ventricular volume characteristics in tetralogy of Fallot and their relationship to arterial oxygen saturation and age

Left (LV) and right ventricular (RV) volume characteristics in 43 patients with tetralogy of Fallot (TOF) undergoing no prior surgical intervention, aged 3–50 months, were evaluated. The control group consisted of 45 patients with Kawasaki disease without cardiac lesions, aged 12–82 months. The TOF patients were divided into four groups: those having arterial oxygen saturation < 80% with an age at the time of study < 18 months (group 1a) or with that ≧ 18 months (group 1b), and those with arterial oxygen saturation ≧ 80% with an age < 18 months (group 2a) or with that ≧ 18 months (group 2b). The results were compared with those in control subjects. In group 1a, each of LV end-diastolic volume (EDV), LV ejection fraction (EF), RVEDV and RVEF was reduced. In group 1b, LVEDV, LVEF and RVEF were decreased. In groups 2a and 2b, RVEF alone was depressed. From these results, the severity of hypoxemia was an important risk factor for ventricular dysfunctions. No influence of age on the volume characteristics was found. The investigations suggested that patients with TOF having an arterial oxygen saturation < 80% are probably candidates for early surgical intervention.     

Studies on peptides

A decapeptide corresponding to the entire amino acid sequence of neurokinin A, a porcine spinal cord peptide, was synthesized in a conventional manner using protecting groups removable by 1 M TFMSA-thioanisole in TFA. The HS-CH₂CH₂CO group was introduced onto the synthetic neurokinin A by reaction of 3-(S-acetyl-thiopropionyl)-thiazolidine-2-thione, followed by deacetylation with hydroxylamine. 2,4-Dinitrophenyl-p-(β-nitrovinyl)-benzoate trapped the above HS-CH₂CH₂CO-neurokinin A derivative in acidic media, then BSA in basic media in nearly quantitative yield. A similar decapeptide, neurokinin B, was also synthesized and conjugated onto BSA using an alternative SH-introducing reagent, 3-(S-p-methoxybenzyl-thiopropionyl)-thiazolidine-2-thione, and the above heterobifunctional conjugating reagent.     

Partial trisomy for short arm of chromosome 5

We present two unrelated cases of partial trisomy for the short arm of chromosome 5, the first such cases reported in Japan. The features are characterized by hypertelorism, low set ears, arachnodactyly, laryngostenosis, hypotonia and some cerebral malformation. The characteristic facial expression and arachnodactyly are the key features used to diagnose this disorder. A high-resolution chromosome banding technique showed that the karyotype of the first patient was 46, XX, inv dup(5) (p13.1 ← p15.3) de novo and that of the second patient was 46, XX, dir dup(5) (p13.3 ← p15.2) de novo. The similar symptoms in the two cases, despite the difference in karyotypes, were caused by duplication of 5p including segment 5p13. This would be a key site for this disorder.