Reversible CD8 expression induced by common cytokine receptor gamma chain-dependent cytokines in a cloned CD4(+) T(h)1 cell line

T cells that are intrathymically lineage committed are believed to maintain their CD4 or CD8 co-receptor expression. Here, we investigated whether intrathymic lineage commitment involves irreversible genetic modification or whether co-receptor expression can be reprogrammed depending on external stimuli. The CD4(+) T(h)1 clone 2D6 established from splenic T cells as an IL-12-dependent line survived in culture with IL-2, IL-7 or IL-15 alone. Surprisingly, CD8 expression occurred in 2D6 cells upon replacement of IL-12 with any one of the three cytokines that stimulate the common cytokine receptor gamma chain, yielding CD4(+)CD8(+) 2D6 cells. CD8 expression declined when IL-2 was replaced with IL-12 and CD8 induction was inhibited when IL-12 was included in IL-2 or IL-7 culture. Our observations show that even a lineage-committed mature T cell can be reprogrammed for co-receptor expression in response to particular external stimuli.     

Association of beta-fibrinogen and factor VII polymorphism with plasma fibrinogen and factor VII levels,and no association of PAI-1 polymorphism with plasma PAI-1 levels in hemodialysis patients

AIMS: Recent studies have stressed the roles of genetic factors on the plasma levels of hemostatic markers and on cardiovascular complications. We investigated the association of DNA polymorphisms for beta-fibrinogen, factor VII, and PAI-1 with plasma levels of these factors and with ischemic heart disease (IHD) and cerebral infarction (CI) in patients undergoing hemodialysis (HD). METHODS: beta-fibrinogen G/A-455, factor VII R353Q and PAI-1 4G/5G polymorphisms were determined by PCR-RFLP in 149 HD patients and in 100 controls. The plasma levels of fibrinogen, factor VII and PAI-1 were also measured. RESULTS: The allele frequencies and the genotype frequencies of these 3 polymorphisms were not different between HD patients and controls. In HD patients, plasma fibrinogen levels were significantly lower in the GG genotype than in the GA genotype, and plasma factor VII activity was significantly higher in the RR genotype than in the RQ genotype. Multiple regression analysis disclosed that CRP and beta-fibrinogen polymorphism were the significant determinants of fibrinogen levels. Plasma PAI-1 levels were not different among the 3 genotypes. The frequency of the A-455 allele was significantly higher in HD patients with CI than in those without CI, and the genotype distribution for beta-fibrinogen differed significantly between the 2 groups. Between the same 2 groups, however, significant differences were found neither in the frequency of the 353Q or 4G allele nor in the genotype distribution for factor VII and PAI-1. No significant differences in the frequency of the G-455, 353Q or 4G alleles, or in the genotype distribution for beta-fibrinogen, factor VII and PAI-1 were observed between patients with IHD and those without IHD. Multiple logistic regression analysis demonstrated that neither polymorphism was associated with CI or IHD. CONCLUSIONS: In HD patients, beta-fibrinogen and factor VII polymorphisms affected plasma levels of fibrinogen and factor VII, respectively. Beta-fibrinogen polymorphism was not an independent but a possible risk factor for CI in HD patients. Further study will be needed to confirm the precise role of 5-fibrinogen polymorphisms in the pathogenesis of CI in HD patients.     

Usefulness of three-dimensional MR images of brain tumors for surgical simulation

The purpose of this study was to determine the usefulness of three-dimensional (3D) MR imaging of brain tumors for surgical planning. Sixty-nine patients with various tumors of the brain were included in the present study. Using a volume-rendering (VR) method on an independent workstation, 3D-MR images were obtained with the fast-SPGR sequence after Gd-DTPA administration. VR images could show an exact relationship between the surface of the brain and major vessels. However, in patients with deeply located tumors, VR images did not necessarily provide sufficient information as to the relationship between the tumor and vessels. In combination with a surface-rendering method, 3D-MR imaging could demonstrate the exact relationships among the tumors, major vessels, and surface of the brain. In tumors without contrast enhancement, this method was able to show 3D images of tumors with surrounding structures. For neurosurgeons, 3D-MR images were useful for understanding the surface anatomy and surrounding structures of the tumors prior to surgery. These images were also helpful in explaining the condition of the disease to patients and their families.     

Treated hypertensives with good medication compliance are still in a state of uncontrolled blood pressure in the Japanese elderly

Objectives Blood pressure (BP) is poorly controlled in many countries. Poor compliance was suggested as the main cause for poor BP control. The purpose of this study was to examine the association between compliance and the control of both casual blood pressure (BP) and 24-hr ambulatory BP in a Japanese elderly population. Methods The study was a cross-sectional survey. Casual BP and 24-hr ambulatory BP were measured at home. Hypertension was defined as casual systolic BP (SBP)≧140 and/or diastolic BP (DBP)≧90 mmHg, or as treated hypertension. A compliance rate of greater than 80% by the pill count method was defined as good compliance. Results Of the 178 treated hypertensives, 82.6% showed good compliance. Between the treated hypertensives with good compliance and those with poor compliance, no significant difference was found in either casual BP or ambulatory BP. Of the treated hypertensives with good compliance, the prevalence of achieved target ambulatory BP, i.e., daytime BP<135/85 mmHg, nighttime BP<120/75 mmHg, and 24-hr BP<125/80 mmHg, was, respectively, 35.4%, 43.5%, and 20.4%. Conclusions Casual BP and 24-hr ambulatory BP were poorly controlled in the community-living elderly although many of the treated hypertensives showed good compliance. It is unlikely that this inadequate control of hypertension is due to poor compliance on the part of the subjects.     

Vasopressin increases vascular endothelial growth factor secretion from human vascular smooth muscle cells

Vascular endothelial growth factor (VEGF) is a potent and specific mitogen of vascular endothelial cells which promotes neovascularization in vitro. To determine whether vasopressin induces VEGF secretion in human vascular smooth muscle cells, we performed enzyme-linked immunosorbent assays. Vasopressin potently induced a time-dependent and concentration-dependent (maximal, 10(-7) M) increase in VEGF secretion by human vascular smooth muscle cells that was maximal after 24 h. Furthermore, vasopressin also concentration-dependently caused mitogenic effect, as reflected by total protein content of cells per culture well. These vasopressin-induced VEGF secretion increase and mitogenic effect of these cells were potently inhibited by vasopressin V1A receptor antagonists, confirming this is a vasopressin V1A receptor-mediated event. These results indicate that vasopressin increases VEGF secretion in human vascular smooth muscle cells, the magnitude of VEGF secretion being temporally related to the mitogenic effect of vascular smooth muscle cells and the potency of the growth-promoting stimulus. Vasopressin-induced VEGF secretion by proliferating vascular smooth muscle cells could act as a paracrine hormone to powerfully influence the permeability and growth of the overlying vascular endothelium, vasopressin play a more fundamental role in the regulation of vascular function than has previously been recognized.     

Comparison of vasopressin binding sites in human uterine and vascular smooth muscle cells.

Several studies indicate that oxytocin and vasopressin receptors in the human uterus are heterogeneous. We have investigated whether oxytocin and vasopressin bind to separate receptors or one class of receptors in human uterine smooth muscle cells. [3H]d(CH2)5Tyr(Me)AVP, the vasopressin V1A receptor selective radioligand, was used for comparison of vasopressin binding sites in human uterine and vascular smooth muscle cell membranes. Both membrane preparations exhibited one class of high-affinity binding sites with Kd values of 6.44 and 0.47 nM, Bmax values of 166 and 34.8 fmol/mg protein for uterine and vascular smooth muscle cells, respectively. In vascular preparations, the selective vasopressin V1A receptor antagonist, SR 49059 ((2S) 1-[(2R 3S)-(5-chloro-3-(2-chlorophenyl)- -(3.4-dimethoxybenzenesulfonyl)-3-hydroxy-2,3-dihydro-1H-indole-2- carbonyl]-pyrrolidine-2-carboxamide), showed high affinity with Ki value of 0.98 nM, confirming that these receptors belong to the vasopressin V1A receptor subtype. On the contrary, in uterine preparations, binding of [3H]d(CH2)5Tyr(Me)AVP was more effectively displaced by oxytocin and the oxytocin receptor selective antagonist, L-371257, (1-[1-[4-[ N-Acetyl-4-piperidinyl)oxy]2-methoxybenzoyl]piperidin-4-yl]- 4H-3,1-benzoxazin-2(1H)-one), than vasopressin and SR 49059, suggesting that binding may be due to cross-reaction with the oxytocin receptors. These results suggest that human uterine smooth muscle cells express only a high density of oxytocin receptors.     

Positron emission tomographic assessment of cerebral hemocirculation and glucose metabolism in malignant glioma following treatment with intracarotid recombinant human tumor necrosis factor-α

Summary Cerebral hemocirculation and glucose metabolism in a malignant astrocytoma were repeatedly quantified before and after intracarotid injection of recombinant human tumor necrosis factor- (rH-TNF) using positron emission tomography (PET). The patient received an intracarotid injection of a 3 × 10⁴ U/m² dose of rH-TNF three times over a two week period. PET was performed prior to and 24 hr after the first injection, and two weeks after the third injection. Prior to the first rH-TNF treatment, two lesions demonstrating high perfusion and hypermetabolism of glucose were noted in the right frontal and temporal regions. The frontal hypermetabolic lesion showed decreases in hemocirculation and metabolism 24 hr after the first injection and then increases beyond the pre-treatment level two weeks after the third treatment, whereas the temporal lesion remained unchanged during the follow-up period. No appreciable changes were noted in the adjacent cortex where rH-TNF was perfused, with the exception of a transient decrease in regional blood volume. Magnetic resonance images of the tumor showed no changes as a result of treatment with intracarotid rH-TNF. Intracarotid rH-TNF preferentially affects tumor tissue as opposed to normal cortex.     

Biophysical characteristics of HIMAC clinical irradiation system for heavy-ion radiation therapy

PURPOSE: The irradiation system and biophysical characteristics of carbon beams are examined regarding radiation therapy. METHODS AND MATERIALS: An irradiation system was developed for heavy-ion radiotherapy. Wobbler magnets and a scatterer were used for flattening the radiation field. A patient-positioning system using X ray and image intensifiers was also installed in the irradiation system. The depth-dose distributions of the carbon beams were modified to make a spread-out Bragg peak, which was designed based on the biophysical characteristics of monoenergetic beams. A dosimetry system for heavy-ion radiotherapy was established to deliver heavy-ion doses safely to the patients according to the treatment planning. A carbon beam of 80 keV/microm in the spread-out Bragg peak was found to be equivalent in biological responses to the neutron beam that is produced at cyclotron facility in National Institute Radiological Sciences (NIRS) by bombarding 30-MeV deuteron beam on beryllium target. The fractionation schedule of the NIRS neutron therapy was adapted for the first clinical trials using carbon beams. RESULTS: Carbon beams, 290, 350, and 400 MeV/u, were used for a clinical trial from June of 1994. Over 300 patients have already been treated by this irradiation system by the end of 1997.     

Wakame Seaweed Suppresses the Proliferation of 7,12-Dimethylbenz(a)-anthracene-induced Mammary Tumors in Rats

We examined the anti-tumor proliferation effects of wakame seaweed on 7,12-dimethylbenz(a)-anthracene (DMBA)-induced rat mammary tumor. DMBA was administered to 8-week-old female Sprague-Dawley rats, and rats which developed mammary tumors were assigned randomly to three groups. Commercial rat feed was used in a control group (group I-A), and two feed mixtures were prepared, which contained commercial rat feed blended with wakame at 1.0% (group I-B) and 5.0% (group I-C) by weight. The respective feeds were given to each group for 8 weeks, and changes in mammary tumor size were compared. At the end of the experiment, mammary tumors and thyroid glands were resected to compare their weights. Serum total iodine and thyroxin (T4) levels were measured. Immunohistochemical studies for bromodeoxyuridine (BrdU) labeling, transforming growth factor (TGF)-β, and apoptosis were carried out in the resected tumor. Significant suppression of tumor growth was observed in groups I-B and I-C compared with I-A. In groups I-B and I-C, the weights of resected mammary tumors were significantly lower and serum total iodine concentration was significantly higher than in I-A. BrdU indices were significantly lower in groups I-B and I-C, compared with I-A. TGF-β and apoptotic index were inversely related to BrdU. These results suggest that iodine is transported from the serum into mammary tissues and induces apoptosis through the expression of TGF-β. In conclusion, wakame suppressed the proliferation of DMBA-induced mammary tumors.