Extensive and coincident side branching of dentinal tubules

Slices of decalcified cat's canine teeth were impregnated with silver nitrate. The stain was taken up by the dentinal tubules. In sections 100 microns thick cut parallel to the long axis of the tooth, dark staining lines were seen running at right angles to the dentinal tubules. Examination at higher power and in thinner sections showed this appearance to be due to the coincident side branching of dentinal tubules. The side branches anastomosed and formed a series of lateral channels in the dentine. These channels may allow for the lateral spread of dentinal caries and of stimuli applied to the peripheral dentine.     

Pharmacological evidence for stimulation of growth hormone secretion by a central noradrenergic system in dogs

The role of brain catecholamines in the regulation of growth hormone secretion was investigated in pentobarbital-anesthetized dogs by using drugs which modify the function of adrenergic neurons and receptors. Intravenous administration of L-dopa produced a prompt, statistically significant increase in plasma growth hormone concentration. This response was not significantly reduced by blockade of peripheral dopa decarboxylase activity with carbidopa. Clonidine, an alpha-agonist which penetrates the brain, increased plasma growth hormone secretion. Norepinephrine, epinephrine, dopamine and isoproterenol, catecholamines which do not penetrate the blood-brain barrier, failed to affect plasma growth hormone concentration when administered intravenously. Apomorphine did not produce a statistically significant increase in plasma growth hormone concentration when administered directly into the the third ventricle, and pimozide failed to abolish the increase in plasma growth hormone produced by L-dopa. The increase in plasma growth hormone concentration produced by intravenous L-dopa and clonidine was prevented by administration of phentolamine or phenoxybenzamine directly into the third ventricle. The response to L-dopa was also abolished by intraventricular procaine. In dogs in which central beta-adrenergic blockade was produced by intraventricular L-propranolol, the growth hormone response to L-dopa was greater than it was in control dogs treated with intraventricular D-propranolol. The data indicate that in pentobarbital anesthetized dogs, the increase in growth hormone secretion produced by L-dopa is mediated by norepinephrine, rather than dopamine, that the site of action of the norepinephrine is central, above the median eminence and inside the 'blood-brain barrier', and that the norepinephrine acts via alpha-adrenergic receptors.     

Identification of MEN1 gene mutations in sporadic carcinoid tumors of the lung

Lung carcinoids occur sporadically and rarely in association with multiple endocrine neoplasia type 1 (MEN1). There are no well defined genetic abnormalities known to occur in these tumors. We studied 11 sporadic lung carcinoids for loss of heterozygosity (LOH) at the locus of the MEN1 gene on chromosome 11q13, and for mutations of the MEN1 gene using dideoxy fingerprinting. Additionally, a lung carcinoid from a MEN1 patient was studied. In four of 11 (36%) sporadic tumors, both copies of the MEN1 gene were inactivated. All four tumors showed the presence of a MEN1 gene mutation and loss of the other allele. Observed mutations included a 1 bp insertion, a 1 bp deletion, a 13 bp deletion and a single nucleotide substitution affecting a donor splice site. Each mutation predicts truncation or potentially complete loss of menin. The remaining seven tumors showed neither the presence of a MEN1 gene mutation nor 11q13 LOH. The tumor from the MEN1 patient showed LOH at chromosome 11q13 and a complex germline MEN1 gene mutation. The data implicate the MEN1 gene in the pathogenesis of sporadic lung carcinoids, representing the first defined genetic alteration in these tumors.      

Changes in the lung in Bourneville-Pringle disease--a contribution to the roentgenologic differential diagnosis of interstitial lung processes

Adenoma sebaceum, also known as Pringle's tumour, is frequently associated with tuberous sclerosis (Bourneville's disease); if the lungs are involved, however, the clinical course is different from that of the "classical" type of the combination of these two diseases without lung involvement. The case record of a woman patient in whom the lung was affected, is presented with a brief discussion of the x-ray and pathological changes and their differential diagnosis.     

A randomized trial of high-dose methotrexate versus standard-dose methotrexate following cyclophosphamide, doxorubicin (adriamycin), vincristine, and prednisone with or without bleomycin in the therapy of diffuse large cell lymphoma: preliminary report of Cancer and Leukemia Group B Study 7851

Between 1979 and 1985, 166 patients with diffuse large cell (histiocytic) lymphoma were randomized to receive therapy with 3 courses of cyclophosphamide, doxorubicin (Adriamycin), vincristine, and prednisone (CAVP), with or without low-dose bleomycin, by continuous iv infusion. Responders were further randomized to 3 weeks of therapy with either high-dose methotrexate (3 g/m2 iv weekly with leukovorin rescue) or low-dose methotrexate (30 mg/m2 orally weekly without rescue). Therapy was concluded with 3 additional courses of CAVP. No significant differences among the 4 treatment programs were observed in complete response rates (ranging from 46% to 51%) or in failure-free survival. Of the 38 relapses that have occurred in patients treated with low-dose methotrexate, 5 included relapse in the central nervous system in conjunction with systemic relapse. However, none of 31 relapses observed in patients receiving high-dose methotrexate have occurred with involvement of the central nervous system. Patients entering this study with "B" symptoms had significantly poorer treatment results than those patients entering study without "B" symptoms.     

Increased cancericidal activity of PTT.119; a new synthetic bis-(2-chloroethyl)amino-l-phenylalanine derivative with carrier amino acids

Summary A new synthetic tripeptide (p-F-Phe-m-bis-(2-chloroethyl)amino-Phe-Met ethoxy HCl), PTT.119, was demonstrated to have significant cancericidal activity against seven in vitro tumor cell lines of different origins and etiologies and against primary human AMML, ALL, and hairy cell leukemias. Viabilities of each murine tumor and rabbit, marmoset, and human leukemia and lymphoma line were significantly reduced by treatment with 1–50 g PTT.119 in media containing serum. Continuous 24-h exposure or pulse treatment as short as 15 and 30 min with the tripeptide resulted in irreversible damage to the tumor cells. Under identical treatment conditions, freshly isolated human leukemic cells, particularly ALL lymphoblasts, were even more susceptible to PTT.119 than any of the tested tumor cell models.Examination of the parameters of PTT.119 activity revealed that reductions of tumor cell survival were dependent on the concentration of the tripeptide. Prolongation of PTT.119 exposure from 15 min to 24 h increased the rates of tumor cell death but did not proportionally reduce the numbers of surviving cells. Assessment of tumor cell viabilities for 5 consecutive days following pulse exposure to PTT.119 demonstrated increasing reductions in tumor cell survival, which were greatest 5 days after treatment with the tripeptide.The cancericidal activity of PTT.119 was compared with its three parental components either as individual agents or as a mixture. Both the alkylator moiety, m-sarcolysin (m.L.SL) alone or together with p-fluoro-phenylalanine and l-methionine ethoxy HCl, and l-PAM (l-phenylalanine mustard), the p-isomer of m.L.SL, were 1.5- to 3-fold less cytotoxic to L1210 leukemia and MJY-alpha mammary tumor cells than PTT.119. Covalent linkage of the amino acid residues to m.L.SL yielded a molecule with greatly augmented cancericidal activity capable of acting against a broad spectrum of tumor cells.     

Does Perceived Quality of Care Moderate Postpartum Depression? A Secondary Analysis of a Two-Stage Survey

Maternal and Child Health Journal - The purpose of this study was to examine if women’s perceptions of the quality of hospital care during childbirth moderate their risks for symptoms of...