[Current status of clinical pharmacology in the United States].
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Biomedical subjects
Publications and source records attributed to T Tanabe.
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Three cases of bleeding esophageal varices associated with arteriovenous malformation of the pancreas have been observed over the last 7 years. In 1 case, arteriovenous malformation (AVM) was the cause of the portal hypertension; thus, it was considered to be a "primary lesion." In the other cases, liver cirrhosis was the cause of the portal hypertension, and the AVM, which originally was a minor pathology, became significant as the portal hypertension progressed, thus making it a "secondary lesion." In the case of a "primary lesion," resection of the lesion is the preferred treatment for bleeding varices, but our case had multiple lesions, and excision was problematic. In the case of bleeding varices caused by liver cirrhosis, if liver function is normal, surgical treatment of both the varices and the AVM is recommended, while if the liver function is abnormal, repeated sclerotherapy is the best mode of therapy.
BACKGROUND: The term "junctional parenchyma" (JP) has been used to represent many renal anomalies including lobar dysmorphism; however, it has not been evaluated with modalities other than ultrasound (US). METHODS: Twenty-two kidneys with lobar dysmorphism incidentally found on helical computed tomography (CT) were studied. In all cases, axial, multiplanar reformation, and three-dimensional images on corticomedullary phase scans were analyzed. Fifteen additional kidneys were prospectively examined with US, and we compared those sonograms with helical CT findings. RESULTS: Comparison of the US and helical CT findings showed that the JP defect and the JP line corresponded anatomically to the upper aspect of the renal sinus and to the thick mural cortex originating from that point, extending inferiorly, respectively. The lesions of lobar dysmorphism were situated deep in the medulla, adjacent to the cortex; however, findings on helical CT did not indicate JP. CONCLUSIONS: Although JP may have been seen on US in this study, it did not show fusion remnants of subkidneys but a combination of the upper aspect of the renal sinus, the mural cortex, and the lesion of lobar dysmorphism.
Eighty-seven consecutive patients were treated with an open Bankart repair for traumatic, recurrent anterior instability of the shoulder. Forty-six of these patients underwent a transosseous suture technique. Forty-one patients were operated on with suture anchors. After follow-ups that ranged from 18 to 85 months, 7 of the 87 patients showed signs of recurrence and another 14 patients reported apprehension. Compared with the 66 patients without residual instability, these 21 patients were more likely to have been operated on with suture anchors (P < .05), had a greater incidence of hypermobility in joints other than the shoulder (P < .05), and had had a greater number of preoperative episodes (P < .05). In light of this data we recommend the transosseous suture technique for open Bankart repairs. In addition, a cautious and extensive capsular repair may be required when a patient reports frequent subluxations preoperatively or has hypermobility in some joints, if not in the shoulder per se.
The nicotinic acetylcholine receptor (AChR) from fish electric organ is well characterized and is known to consist of five subunits present in a molar stoichiometry of alpha 2 beta gamma delta (reviewed in refs 1-3). The mammalian skeletal muscle AChR is thought to have a similar subunit structure. We have recently elucidated the primary structures of the alpha-, beta-, gamma- and delta-subunit precursors of the Torpedo californica AChR by cloning and sequencing cDNAs for these polypeptides; cDNA sequences for the gamma-subunit precursor of the T. californica AChR and the alpha-subunit precursor of the Torpedo marmorata AChR have also been reported by other groups. The four subunits exhibit conspicuous sequence homology and are similar in hydrophilicity profile and predicted secondary structure, thus being most probably oriented in a pseudosymmetric fashion across the membrane. The transmembrane topology of the subunit molecules and the locations of functionally important regions, such as the acetylcholine binding site and the trans-membrane segments which may be involved in the ionic channel, have been proposed. We have now cloned cDNA for the alpha-subunit precursor of the calf skeletal muscle AChR and a human genomic DNA segment containing the corresponding gene. Nucleotide sequence analysis of the cloned DNAs has revealed the primary structures of the calf and human AChR alpha-subunit precursors, which exhibit marked sequence homology with their Torpedo counterpart. The protein-coding sequence of the human AChR alpha-subunit precursor gene is divided by eight introns into nine exons, which seem to correspond to different structural and functional domains of the subunit precursor molecule.
Cloning and sequence analysis of cDNA for the Electrophorus electricus electroplax sodium channel indicate that this protein, consisting of 1,820 amino acid residues, exhibits four repeated homology units, which are presumably oriented in a pseudosymmetric fashion across the membrane. Each homology unit contains a unique segment with clustered positively charged residues, which may be involved in the gating structure, possibly in conjunction with negatively charged residues clustered elsewhere.
A group of membrane-associated guanine nucleotide binding proteins (G-proteins) are essential for transducing signals generated at cell-surface receptors into changes in cellular function and metabolism. These proteins are a complex of three subunits designated alpha, beta and gamma. The alpha-subunit is responsible for binding guanine nucleotides and seems to be characteristic of each protein. Transducin, a member of this protein family, mediates visual transduction by coupling the signal of photolysed rhodopsin with activation of a cyclic GMP phosphodiesterase. We have now cloned and sequenced the complementary DNA encoding the alpha-subunit of bovine retinal transducin and from this we have deduced the complete amino-acid sequence. The transducin alpha-subunit shares several homologous amino-acid sequences with ras gene products. The homologous segments correspond mostly to the regions thought to be involved in the guanine nucleotide binding and GTPase activity of ras proteins and to the ADP-ribosylation sites of the transducin alpha-subunit.
Complementary DNA encoding the IgG1 induction factor, the first lymphokine directed to B lymphocytes, from a murine T-cell line has been cloned using a new strategy. The putative primary amino-acid sequence was deduced from the nucleotide sequence determined. The lymphokine synthesized by the direction of this cloned cDNA has many other functions, such as production of B-cell growth factor-1 and induction of Ia on B cells.
Proliferation and maturation of antigen-stimulated B cells are regulated by several soluble factors derived from macrophages and T cells. These soluble factors are functionally divided into two groups: B-cell growth factor (BCGF), thought to be involved in B-cell proliferation; and B-cell differentiation factor (BCDF), responsible for maturation of activated B cells into immunoglobulin-secreting cells. This classification needs to be re-examined in the light of the recent cloning of complementary DNA encoding IgG1 induction factor (interleukin-4, IL-4) from the 2.19 mouse T-cell line. Recombinant IL-4 has BCGF and BCDF activities and affects B cells, T cells and mast cells (refs 7, 8; our unpublished data). Another well-characterized B-cell factor is T-cell replacing factor (TRF), which, when secreted by the murine T-cell hybridoma B151K12, is defined by two activities: induction of IgM secretion by BCL1 leukaemic B-cell line; and induction of secondary anti-dinitrophenol (DNP) immunoglobulin G (IgG) synthesis in vitro by DNP-prime B cells. Although TRF from B151K12 was classified as BCDF, purified TRF has BCGF-II activity. To elucidate the molecular properties of TRF we isolated cDNA encoding TRF from the 2.19 T-cell line and report here the structure and multiple activities of this lymphokine.
The complete amino-acid sequence of the receptor for dihydropyridine calcium channel blockers from rabbit skeletal muscle is predicted by cloning and sequence analysis of DNA complementary to its messenger RNA. Structural and sequence similarities to the voltage-dependent sodium channel suggest that in the transverse tubule membrane of skeletal muscle the dihydropyridine receptor may act both as voltage sensor in excitation-contraction coupling and as a calcium channel.
Mass screening for liver cancer based mainly on abdominal ultrasound was begun in major cities of Hokkaido, Japan, in November 1981, to enable early detection and treatment of hepatocellular carcinoma (HCC). Serum alpha-fetoprotein levels were also measured to minimize false negative studies. Examinees included those who sought liver disease screening as well as high risk individuals: hepatitis B surface antigen carriers and those with a past or current liver disease, history of blood transfusion, family history of liver cancer, and more recently those with positive anti-hepatitis C antibodies. The examination was carried out on each Saturday and Sunday as one round, and by February 1992 48 rounds had been performed. A total of 8090 individuals were investigated, and HCC was detected in 91 with a detection rate of 1.12%. This rate was 1.6% among 5684 individuals who were selected for high risk. Cumulative rates of survival among these patients were 79.0% at 1 year, 43.8% at 3 years, 19.3% at 5 years and 15.4% at 7 years. These survival rates were comparable with those for the patients with HCC diagnosed during follow-up of chronic liver disease and treated at our hospital. The cost for detecting one HCC patient in this programme was 2,660,000 yen (approximately US$25,000), which was less than those for some other types of cancer in a similar setting. Considering the high detection rate in this programme, we feel that similar programmes should be encouraged and supported.
BACKGROUND: Although incidence of ventricular arrhythmias after partial left ventriculectomy (PLV) has been reported, there are no studies comparing incidence before and after PLV. Although operative scars may give rise to arrhythmias, improved energetic efficiency after PLV may decrease their incidence. METHODS: Pre- and postoperative ventricular arrhythmias were monitored by Holter ECG and analyzed in 17 patients undergoing PLV in Curitiba, Brazil. RESULTS: Although total 24-hour heart beat (THB) increased significantly (p = 0.018), ventricular premature contractions (VPCs) decreased markedly (p = 0.036), excluding one patient dying in low cardiac output (LOS) who had terminal arrhythmias increased multifold. In the remaining 16 patients, VPC pairs were also reduced significantly on the average (p = 0.038). In contrast, ventricular tachycardia (VT; more than three consecutive VPCs) disappeared in five patients, decreased in two patients, and newly occurred in four patients, with five patients showing no change; one of them developed a prolonged VT, successfully reversed by external cardioversion. CONCLUSIONS: Despite notable significant increase in THB immediately after PLV, PVC and PVC pairs were significantly decreased in contrast to VT, which disappeared in some patients and newly occurred in other patients, remaining constant on the average. Sustained VT occurring in a patient with all other arrhythmias suppressed may suggest a unique electrophysiological substrate, may justify prophylactic use of amiodarone or an implantable cardioverter-defibrillator, and may underscore the importance of further and extended studies.
We studied the production of macrophage colony-stimulating factor (M-CSF) and the expression of c-fms mRNA, an M-CSF receptor, in four human ovarian cancer cell lines. All four cell lines expressed c-fms mRNA while three secreted M-CSF into the culture medium. The exogenous administration of M-CSF caused no significant enhancement of cellular proliferation in any cell line. Interestingly, the proliferation of KK cells was not affected by anti-M-CSF antibody. These results, taken together with the fact that ovarian cancer cells simultaneously produce M-CSF and c-fms, suggest that an autocrine mechanism may modulate cellular proliferation.
PURPOSE: Report of a case with retinal neovascularization developing in the setting of diabetic retinopathy despite complete posterior vitreous detachment (PVD). CASE REPORT: A 76-year-old man had had type II diabetes mellitus for more than 30 years. Weiss' ring was detected by direct and indirect ophthalmoscopy. PVD was thus considered to be complete. On the other hand, fluorescein angiography showed two areas of hyperfluorescence at the margin of the retinal nonperfusion area. CONCLUSIONS: The present case underscores the importance of periodic follow-up using fluorescein angiography, given the probability of retinal neovascularization development and proliferative changes for many years even in diabetic retinopathy associated with complete PVD.