Biomedical subjects
Publications and source records attributed to D Nakayama.
We report a case of monozygotic twins. One twin had a single umbilical artery and the other co-twin had congenital heart disease. This case and a review of the literature suggest that local environmental factors are important in the pathogenesis of these malformations although genetic factors cannot be excluded.
Explore the source record for details and available documents.
An 8-year-old girl had a 5-month history of recurrent rectal prolapse. On colonoscopy, two submucosal masses were noted in the distal rectum and diagnosed by biopsy as benign lymphoid hyperplasia. These were excised by limited dissection superficial to the submucosa, and the histologic diagnosis was confirmed. The child has done well after removal of the nodules, with no subsequent prolapse for more than 2 years.
In utero somatic gene transfer may be a useful therapeutic strategy for a variety of inherited disorders. In the present study, we demonstrate transgene expression in the airways of fetal lamb lungs, 2-3 weeks after injection of Moloney murine leukemia retrovirus based vectors containing cDNA for beta-galactosidase (lacZ) or human interleukin receptor antagonist protein (IRAP), into the fluid filled future airspace of fully catheterized twin fetal lambs (104-117 days gestational age; term 147 days). Expression of lacZ or IRAP was limited to the twin that received the respective vector and was apparent, at light microscopic level, in the epithelium and submucosal space of proximal airways, and to a lesser extent, in the respiratory epithelium of the distal airways. These data demonstrate for the first time that transfer of foreign DNA to fetal lung can be accomplished. These findings support the use of retroviral vectors for somatic lung DNA transfer and suggest that inherited disorders such as cystic fibrosis may be approached therapeutically via gene transfer, in utero.
By analysing a genomic DNA clone derived from the human T cell lymphotropic virus type 1 (HTLV-1)-infected cell line, TL-Su, we found that an integrated HTLV-1 provirus interrupted the poly(A) signal-containing exon of a novel gene, RY-1. Nucleotide sequence analysis of a cDNA derived from Jurkat cells revealed that the normal RY-1 mRNA could encode a novel protein that has an unique primary structure, suggesting that a nucleic acid binding property was involved. Proviral integration led to an accumulation of aberrant RY-1 mRNA species in the cells. All the aberrant RY-1 cDNAs derived from TL-Su cells terminated at the poly(A) site of the R region of the HTLV-1 long terminal repeat and initiated in the intron, approx. 800 bp upstream from the putative second exon. Furthermore, another intron, downstream from this position, remained unspliced in some of the cDNAs. In addition to the activation by the integrated viral elements of cryptic promoters located upstream, mechanisms involving altered rates of degradation or transport from the nucleus to the cytoplasm of intron-containing RNA were suggested.
Fatal hematemesis occurred in a 3-month-old boy due to erosion by a nasogastric tube into the right component of an unrecognized double aortic arch. This is the youngest of six reported patients with arterioesophageal fistula in the literature. Including this patient, five of six had nasogastric tubes in place. The tube may have led to fistula formation by compression of the esophageal wall against an anomalous vessel. When a vascular ring is suspected, indwelling esophageal tubes such as nasogastric tubes should not be used.
Accidental injury in a child is sudden, often violent, and emotionally stressful, particularly when it is accompanied by hospitalization and rehabilitation. The following case report examines the presence of post-traumatic stress disorder and other psychiatric illnesses in five children involved in a boating accident during the 1988 Pittsburgh Regatta and considered severity of injury as well as complicating psychosocial stressors in the development of the disorders. The presence of symptoms was not related to the nature or extent of the injury but was instead the by-product of additional factors, including level of family stress, coping styles of the patient and family, positive psychiatric history in the child and/or family, and experience in effectively dealing with stressful episodes in the past.
We studied DNA sequences homologous to HTLV-1 in peripheral blood mononuclear cells (PBMC) of 30 patients with neurological disorders in Kyushu, where HTLV-1 is highly endemic. The regions of HTLV-1 amplified by means of polymerase chain reaction (PCR) included U3, U5, gag, pol, env and pX. Our system specifically detected HTLV-1 sequences only from HTLV-1-positive cells and was sufficiently sensitive to detect one proviral copy per 10(3) PBMC. All PCR-positive cases were seropositive, including 4 cases of tropical spastic paraparesis/HTLV-1-associated myelopathy (TSP/HAM) (4/4), and one case each of myasthenia gravis (1/7) and multiple sclerosis (1/8). The PCR-positive rate of patients, excluding 4 TSP/HAM cases, was 8% (2/26), which is similar to the seroprevalence of the adult population in the area. The data suggest that multiple sclerosis is not associated with prototype HTLV-1.
Transforming growth factor beta 1 (TGF-beta 1) is a potent autocrine growth inhibitor of lymphocytes. In this study, the expression of TGF-beta 1 binding proteins was characterized on murine splenic T cells. With an affinity cross-linking method and by neutralizing antibodies to TGF-beta 1, [125I] TGF-beta 1 was found to bind to three cell surface-binding proteins (280-200 kD, 95-85 kD, 65 kD) that were differentially expressed on resting and mitogen-stimulated T cells. Freshly prepared (resting) T cells were found to constitutively express the 95-85-kD form of these binding proteins, whereas mitogenic stimulation by either concanavalin-A (Con-A), interleukin-1 (IL-1), interleukin-2 (IL-2), or 12-tetradecanoyl-phorbol-13-acetate (TPA) for 12-72 h induced the appearance of all forms of the TGF-beta 1 binding proteins (280-200 kD, 95-85 kD, and 65 kD). Furthermore, antibodies that neutralized the biologic action of TGF-beta 1 also blocked the binding of [125I] TGF-beta 1 to all three binding proteins, suggesting that these binding proteins are involved with signal transduction. These results suggest that the expression of the TGF-beta 1 receptor on T cells is regulated by T cell mitogenic signals and that a regulatory relationship may exist between T cell growth-promoting cytokines (IL-1 and IL-2) and the T cell growth inhibitor, TGF-beta 1.
A crossover study was planned in order to compare the effects of captopril and slow channel calcium entry blocker (Ca antagonist) on urinary protein excretion in 7 hypertensive patients with renal diseases, including 4 with IgA nephropathy, 2 with lupus nephritis and 1 with benign nephrosclerosis. Captopril decreased urinary protein excretion by 52% without any change in creatinine clearance, while Ca antagonist was having a slight effect on proteinuria even though the drug showed an equivalent antihypertensive effect as captopril. These results suggest that the attenuation of proteinuria induced by captopril may be related to an inhibition of angiotensin II formation and/or a direct action of this drug on protein permeability of glomerular basement membrane.
Explore the source record for details and available documents.
The effects of two forms of transforming growth factor-beta, TGF-beta 1 and TGF-beta 2, upon the proliferative response of murine thymocytes were investigated in this study. TGF-beta 1 and TGF-beta 2 were found to be equipotent growth inhibitors of interleukin-1 (IL-1)- and phytohemagglutinin (PHA)-stimulated thymocytes when added at the initiation of the cultures. These factors suppressed the proliferative response in a dose-dependent fashion between 0.4 and 100 pM. The proliferative response was maximally inhibited (90% inhibition) at 100 pM. The half-maximal inhibitory dose (ID50) was 6 and 4 pM for TGF-beta 1 and TGF-beta 2, respectively. These factors were less effective or ineffective at suppressing the proliferation of thymocytes which had been prestimulated for 24 to 48 hr by IL-1 and PHA. Neither factor inhibited interleukin-2 (IL-2)-dependent thymocyte proliferation or the proliferation of an IL-2-dependent cytotoxic T cell line (CTL-L), suggesting that the anti-proliferative actions of these factors was by inhibition of cellular events triggered by IL-1. Furthermore, anti-TGF-beta 1 antibodies did neutralize the biological actions of TGF-beta 1 and these antibodies did block the binding of 125I-labeled TGF-beta 1 to cell surface receptors showing that the inhibitory action is mediated through specific receptors for TGF-beta 1 on thymocytes. These antibodies, however, did not neutralize the anti-proliferative action of TGF-beta 2. Although TGF-beta 1 and TGF-beta 2 exhibit very similar biological activities, these molecules are antigenically different and, therefore, have different tertiary structures.
Effects of guanfacine, a centrally acting antihypertensive, on blood pressure, heart rate, plasma renin activity, serum aldosterone, plasma norepinephrine, and renal function were evaluated in 16 patients with hypertension with biopsy-proved chronic glomerulonephritis. Guanfacine monotherapy with a daily dose of 1 to 2.5 mg at bedtime for 6 months brought about a significant reduction in blood pressure (171 +/- 2/110 +/- 2 to 144 +/- 2/89 +/- 1 mm Hg; P less than 0.01), with concurrent decreases in heart rate (78 +/- 2 to 70 +/- 2 bpm; P less than 0.01), plasma renin activity (1.96 +/- 0.12 to 1.21 +/- 0.19 ng/ml/hr; P less than 0.05), aldosterone (14.6 +/- 1.5 to 9.7 +/- 0.9 ng/dl; P less than 0.05), plasma norepinephrine (220.5 +/- 24.2 to 132.8 +/- 27.7 pg/ml; P less than 0.05). There was no change in serum creatinine, beta 2-microglobulin, or endogenous creatinine clearance during guanfacine monotherapy. Our data suggest that guanfacine exerts its antihypertensive effect via the inhibition of sympathetic outflow and in part the suppression of the reninangiotensin-aldosterone system and that guanfacine is suitable for the effective treatment of hypertension associated with chronic glomerulonephritis.
The ratio of the plasma level of beta-thromboglobulin (beta-TG) to platelet factor 4 (PF-4) which is regarded as a most reliable indicator of platelet activation in vivo, was followed in 52 subjects at various stages of essential hypertension according to the WHO classification. These comprised 30 cases at stage I, 19 cases at stage II and three cases at stage III, and 20 age-matched normotensive control subjects. The observed beta-TG:PF-4 ratio in the hypertensive patients was 4.59 +/- 0.20, which was significantly higher than the value of 3.13 +/- 0.19 recorded in the normotensive control subjects. According to the WHO classification, beta-TG:PF-4 ratios in hypertensive patients at stages I, II and III were 3.93 +/- 0.19, 5.31 +/- 0.35 and 6.56 +/- 0.12, respectively. The beta-TG:PF-4 ratio revealed a tendency of platelet activation to increase with advanced progress of hypertensive vascular lesions. These results suggest that the abnormal platelet function observed in patients with essential hypertension plays an important role in the development of hypertensive vascular complications.
Explore the source record for details and available documents.
Explore the source record for details and available documents.