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PubMed1977

Histocompatibility antigens controlled by the I region of the murine H-2 complex. II. K/D region compatibility is not required for I-region cell-mediated lymphocytotoxicity.

In the cell-mediated lymphocytotoxicity assay, A.TH effector cells sensitized to A.TL lymphocytes lyse not only A.B10.AQR effector cells lyse B10.BR and B10.BYR target cells in addition to B10.AQR cells. These findings indicate that for CML to occur across the IA region barrier, compatibility at K or D regions is not required.

Animals↗
PubMedDate not supplied

Loco-regional renewal of malignant skin melanomas. II. Regional lymph node metastases and regional recurrence.

The strategy of surgical therapy to treat regional disease in melanoma remains still controversial. The author analyzed 154 of 183 melanoma patients, who could be studied for the usefulness of surgery directed against regional tumour spread. Radical tumour excision combined with elective lymph node dissection (E+eRND) in medium or high risk tumour patients was found superior to therapeutic dissection (tRND) inasmuch 5-year-survival rates were significantly different (p < 0.001). Life expectancy seemed to be further impaired when postdissectional renewal appeared following tRND (5-year-survival rates 31.8 per cent --> 12.7 per cent) or tRND was incomplete.

Humans↗
PubMed1992

Regional left ventricular wall thickening. Relation to regional uptake of 18fluorodeoxyglucose and 201Tl in patients with chronic coronary artery disease and left ventricular dysfunction.

BACKGROUND: In previous studies comparing regional 201Tl (201Tl) and 18fluorodeoxyglucose (FDG) activity in patients with chronic coronary artery disease and left ventricular dysfunction, we hypothesized that regions with mild-to-moderate reduction in FDG activity and regions with mild-to-moderate irreversible 201Tl defects after 3- to 4-hour redistribution represent viable myocardium. In the present study, regional FDG and 201Tl activities were compared with regional systolic wall thickening by gated magnetic resonance imaging (MRI) to confirm the presence of viable myocardium in these territories. METHODS AND RESULTS: Twenty-five patients with chronic stable coronary artery disease and left ventricular dysfunction (ejection fraction, 28 +/- 10) underwent exercise 201Tl tomographic imaging (SPECT), using a reinjection protocol, positron emission tomography (PET) with FDG and H2(15)O, and gated MRI. Matched SPECT, PET, and MRI tomograms were analyzed. From the PET data, 105 regions had matched reduction in FDG and blood flow, of which 69 regions had moderately reduced FDG uptake (50-79% uptake relative to a normal reference region) and 36 had severely reduced FDG uptake (less than 50% of normal activity). Regions with moderately reduced as compared with severely reduced FDG activity had greater end-diastolic wall thickness (9.4 +/- 2.6 versus 8.0 +/- 3.7 mm; p less than 0.05) and regional systolic wall thickening (1.7 +/- 2.7 versus -0.7 +/- 2.1 mm; p less than 0.01). From the SPECT data, 169 irreversible 201Tl defects after 3-4 hour redistribution were identified, of which 70 were mild (greater than 65 to less than 85% of maximal 201Tl activity), 52 were moderate (50-65% of maximal activity), and 47 were severe (less than 50% of maximal activity). Regional systolic wall thickening was greater in regions with normal 201Tl uptake (3.3 +/- 2.3 mm) as compared with all other regions. Regions showing only mild or moderate irreversible defects at redistribution, however, showed wall thickening (2.4 +/- 2.4 and 2.2 +/- 2.5 mm, respectively), which was similar to that observed in regions with reversible 201Tl defects (2.1 +/- 2.2 mm). Only regions with severe irreversible defects at redistribution showed absence of thickening (-0.1 +/- 2.9 mm, p less than 0.01 versus all other groups). After 201Tl reinjection, 12 of 47 (26%) regions with severe irreversible defects showed enhanced 201Tl uptake. The impairment in regional systolic wall thickening was not significantly different between 201Tl defects with and without enhanced 201Tl uptake after reinjection. FDG activity, however, was present in all 12 regions (100%) with enhanced 201Tl uptake after reinjection as compared with only five of 35 (14%) that were unchanged after reinjection (p less than 0.01). CONCLUSIONS: Therefore, preserved wall thickness and systolic wall thickening in regions with moderate reduction in blood flow and FDG activity, and in irreversible 201Tl defects that are only mild-to-moderate, provide additional evidence that such regions represent viable myocardium. Moreover, the finding of metabolic activity and 201Tl uptake in regions with reduced blood flow and absent wall thickening provides clinical evidence of hibernating myocardium in humans.

Adult↗
PubMed1980

Activation of secondary cytotoxic lymphocytes by cell-free factors from I-region-primed and D-region-primed lymphocytes.

Cell co-operation in the generation of secondary cytotoxic responses was studied by selectively sensitizing lymphocytes in mixed lymphocyte culture (MLC) across I or D region difference and by combining the primed lymphocytes in the secondary MLC. Secondary cytotoxic responses were induced in D-region-primed lymphocytes by restimulation with the original priming D-region antigens, by co-culturing with the I-region-primed lymphocytes in the presence of the priming I-region antigens, or by cell-free supernatants obtained 24 h after the restimulation of D-region-primed lymphocytes and I-region-primed lymphocytes, The active MLC supernatants produced by both I-region-primed and D-region-primed cells also induced accelerated proliferative responses in D-region-primed lymphocytes. Heat-treatment or ultraviolet irradiation of the stimulator cells eliminated the capacity of the cells to induce the production of CTL-helper factor in I-region-primed and D-region-primed lymphocytes. It was concluded that both I-region-primed and D-region-primed lymphocytes produce a cell-free factor which induces proliferation and secondary cytotoxicity in D-region-primed lymphocytes. The possible participation of D-region reactive helper T cells and D-region reactive cytotoxic T cells in the cytotoxic responses to D-region antigens in the absence of I-region difference is discussed.

Animals↗
PubMed1994

Regional fibre stress-fibre strain area as an estimate of regional blood flow and oxygen demand in the canine heart.

1. In the present study the relation between regional left ventricular contractile work, regional myocardial blood flow and oxygen uptake was assessed during asynchronous electrical activation. 2. In analogy to the use of the pressure-volume area for the estimation of global oxygen demand, the fibre stress-fibre strain area, as assessed regionally, was used to estimate regional oxygen demand. The more often used relation between the pressure-sarcomere length area and regional oxygen demand was also assessed. 3. Experiments were performed in six anaesthetized dogs with open chests. Regional differences in mechanical work were generated by asynchronous electrical activation of the myocardial wall. The ventricles were paced from the right atrium, the left ventricular free wall, the left ventricular apex or the right ventricular outflow tract. Regional fibre strain was measured at the epicardial anterior left ventricular free wall with a two-dimensional video technique. 4. Regional fibre stress was estimated from left ventricular pressure, the ratio of left ventricular cavity volume to wall volume, and regional deformation. Total mechanical power (TMP) was calculated from the fibre stress-fibre strain area (SSA) and the duration of the cardiac cycle (tcycle) using the equation: TMP = SSA/tcycle. Regional myocardial blood flow was measured with radioactive microspheres. Regional oxygen uptake was estimated from regional myocardial blood flow values and arteriovenous differences in oxygen content. 5. During asynchronous electrical activation, total mechanical power, pressure-sarcomere length area, myocardial blood flow and oxygen uptake were significantly lower in early than in late activated regions (P < 0.05). 6. Within the experiments, the correlation between the pressure-sarcomere length area and regional oxygen uptake was not significantly lower than the one between total mechanical power (TMP) and regional oxygen uptake (VO2,reg). However, variability of this relation between the experiments was less for total mechanical power. Pooling all experimental data revealed: VO2,reg = k1 TMP+k2, with k1 = 4.94 +/- 0.31 mol J-1 k2 = 24.2 +/- 1.9 mmol m-3 s-1 (means +/- standard error of the estimate). 7. This relation is in quantitative agreement with previously reported relations between the pressure-volume area and global oxygen demand. The results indicate that asynchronous electrical activation causes a redistribution of mechanical work and oxygen demand and that regional total mechanical power is a better and more general estimate of regional oxygen demand than the regional pressure-sarcomere length area.

Animals↗
PubMed1996

Major role for a 3p21 region and lack of involvement of the t(3;8) breakpoint region in the development of renal cell carcinoma suggested by loss of heterozygosity analysis.

In a loss of heterozygosity analysis of 3p, we examined 44 sporadic cases of renal cell carcinoma (RCC) and matched normal tissue with 18 markers distributed over the whole p-arm. The majority of these markers clustered in three regions that have been suggested to be involved in the development of RCC, namely the p25 region, where the von Hippel Lindau (VHL) gene is located; the p21 region, which has been identified as a common region of overlap (SRO) of heterozygous deletions; and the p14 region, which is the location of the constitutional t(3;8) breakpoint occurring in an RCC family. Thirty-one out of these 44 tumors were analyzed with 9 additional markers from the 3p12-14 region to further delimit the SRO in this region. Our analysis shows that when deletions were detected the 3p21 region was always included. The 3p21 markers D3F15S2 and UBEIL were always contained within these 3p21 deletions. The t(3;8) breakpoint region showed the lowest percentage of loss of heterozygosity. Moreover, in three cases the t(3;8) breakpoint region retained heterozygosity, whereas a region more proximal to the breakpoint showed allelic losses. This supports exclusion of the t(3;8) region from a role in the development of sporadic RCC. In a number of tumors, two or three 3p regions with allelic losses were present separated by a region of retention of heterozygosity. In these tumors, deletions at 3p21 occurred in combination with deletions of either the VHL region, or the region proximal to the t(3;8), or both, suggestive of multiple gene involvement in the development of sporadic RCC with a primary role of the 3p21 region.

Carcinoma, Renal Cell↗
PubMed1985

Distinct H-2-linked regulation of T-cell responses to the pre-S and S regions of the same hepatitis B surface antigen polypeptide allows circumvention of nonresponsiveness to the S region.

Recently, additional polypeptide components of the surface envelope of hepatitis B virus (HBV) have been identified. The pre-S(1) and pre-S(2) regions of the HBV genome encode NH2-terminal amino acid residues that together with the S-gene product (25 kDa) comprise polypeptides of 33 kDa and 39 kDa. The possible immunopathologic significance of these larger polypeptides and their relevance to vaccine development prompted us to examine the murine immune response to pre-S(2)-encoded determinants as compared to S-encoded determinants on the same polypeptide. Previous work showed that the pre-S(2) region elicits greater antibody production in vivo than does the S region of hepatitis B surface antigen. In this study, we examined immunogenicity of the pre-S(2) region at the T-cell level, H-2- and non-H-2-linked genetic influences on the pre-S(2) response, and the effect of the immune response to one region on the immune response to the other region. The results indicate that (i) the pre-S(2) region is significantly more immunogenic than the S region at the T-cell level; (ii) pre-S(2)-region-specific T-cell activation is regulated by H-2-linked genes and correlates with the H-2 restriction of in vivo antibody production to the pre-S(2) region; (iii) the H-2 restriction of the T-cell response to the pre-S(2) region is distinct from the H-2 restriction of the T-cell response to S-region determinants; (iv) non-H-2-linked and non-Igh-linked genes also influence the humoral immune response to the pre-S(2) region; and (v) immunization of an S-region-nonresponder, pre-S(2)-region T-cell-responder strain with HBV envelope particles containing both the pre-S(2) and S regions can circumvent nonresponsiveness to the S region through pre-S(2)-specific T-cell helper function.

Amino Acid Sequence↗
PubMed1988

Integrated regional work equals total left ventricular work in regionally ischemic canine heart.

To assess left ventricular (LV) regional work with physically correct dimensions, wall tension-regional area (T-A) loops were analyzed before and after coronary occlusion in the excised cross-circulated canine LV (n = 11) connected to a volume-servo pump. Wall tension was calculated with the force equilibrium equation for a sphere, and regional areas were determined from pairs of orthogonal sonomicrometers in ischemic and nonischemic regions. LV and regional stroke work were simultaneously assessed from the pressure-volume and T-A loops during one cardiac cycle at various end-diastolic and stroke volumes. After coronary occlusion, regional work of the ischemic region markedly decreased to near or even below zero. Although regional work of the nonischemic region moderately decreased at constant LV end-diastolic and stroke volumes, the contribution of the nonischemic region to LV stroke work increased. Globally integrated regional work calculated from regional work/unit area and estimates of the extent of ischemia closely agreed with measured LV stroke work either before (n = 119; r = 0.92) or after coronary occlusion (n = 141; r = 0.93) despite the marked changes in regional work in both regions. We conclude that the global integral of regional work equals the total LV work and that regional work of the LV can be reliably assessed from the T-A loop with the same dimensions as energy in both normal and regionally ischemic hearts.

Animals↗
PubMed2006

The bacteriophage T4 inhibitor and coactivator AsiA inhibits Escherichia coli RNA Polymerase more rapidly in the absence of sigma70 region 1.1: evidence that region 1.1 stabilizes the interaction between sigma70 and core.

The N-terminal region (region 1.1) of sigma70, the primary sigma subunit of Escherichia coli RNA polymerase, is a negatively charged domain that affects the DNA binding properties of sigma70 regions 2 and 4. Region 1.1 prevents the interaction of free sigma70 with DNA and modulates the formation of stable (open) polymerase/promoter complexes at certain promoters. The bacteriophage T4 AsiA protein is an inhibitor of sigma70-dependent transcription from promoters that require an interaction between sigma70 region 4 and the -35 DNA element and is the coactivator of transcription at T4 MotA-dependent promoters. Like AsiA, the T4 activator MotA also interacts with sigma70 region 4. We have investigated the effect of region 1.1 on AsiA inhibition and MotA/AsiA activation. We show that sigma70 region 1.1 is not required for MotA/AsiA activation at the T4 middle promoter P(uvsX). However, the rate of AsiA inhibition and of MotA/AsiA activation of polymerase is significantly increased when region 1.1 is missing. We also find that RNA polymerase reconstituted with sigma70 that lacks region 1.1 is less stable than polymerase with full-length sigma70. Our previous work has demonstrated that the AsiA-inhibited polymerase is formed when AsiA binds to region 4 of free sigma70 and then the AsiA/sigma70 complex binds to core. Our results suggest that in the absence of region 1.1, there is a shift in the dynamic equilibrium between polymerase holoenzyme and free sigma70 plus core, yielding more free sigma70 at any given time. Thus, the rate of AsiA inhibition and AsiA/MotA activation increases when RNA polymerase lacks region 1.1 because of the increased availability of free sigma70. Previous work has argued both for and against a direct interaction between regions 1.1 and 4. Using an E. coli two-hybrid assay, we do not detect an interaction between these regions. This result supports the idea that the ability of region 1.1 to prevent DNA binding by free sigma70 arises through an indirect effect.

DNA, Bacterial↗
PubMed2000

Esmolol-induced regional wall motion abnormalities do not affect regional ventricular elastances.

UNLABELLED: The effect of regional wall motion abnormalities (RWMA) on regional and global left ventricular (LV) elastances has not been defined. To induce RWMA, we infused esmolol (9 mg) into the left anterior descending coronary artery in eight anesthetized open-chest canine preparations. Global and regional stroke volumes and end-systolic pressure-volume relationships (LV conductance catheter) and pressure-length relationships (sonomicrometer crystals) were measured in dysfunctional (apical) and normal (basilar) LV regions at baseline, during esmolol infusion, and after treatment with a systemic dobutamine infusion (4 microg. kg(-1). min(-1)) and combined dobutamine-esmolol. Esmolol induced apical dyskinesis, as evidenced by reduced effective apical stroke volumes and stroke work, a parallel right-shift of the apical regional, global end-systolic pressure-volume relationships, and increased regional and global LV volumes (P < 0.05). However, global and regional elastances remained unchanged. Dobutamine increased global and apical regional elastances, but did not increase regional volumes. During the infusion of combined esmolol-dobutamine, apical elastance and volumes increased compared with baseline (P < 0.05), but apical regional stroke work decreased. Thus, esmolol-induced RWMA were associated with cardiac dilation but not with decreased regional or global elastances. IMPLICATIONS: Regional and global elastances and maximal stroke volumes may not identify esmolol-induced left ventricular regional dysfunction in dogs. The primary effect of asynchrony of regional contraction is global cardiac dilation. Systemic dobutamine infusion increases regional and global left ventricular elastances but does not reverse regional wall motion abnormality-induced cardiac dilation.

Animals↗
PubMed1987

Quantitative evaluation of left ventricular regional work from wall tension-regional area loop in canine heart.

We evaluated left ventricular (LV) regional work from a wall tension-regional area (T-A) loop using sonomicrometers in the excised cross-circulated canine left ventricle connected to a volume servo pump. Regional work assessed from a T-A loop closely agreed with the predicted value calculated from LV stroke work and percent regional area under conditions of the control state, dobutamine infusion, and global ischemia. In addition, globally integrated regional work over the entire ischemic and non-ischemic zones agreed closely with LV stroke work either before or after coronary occlusion. These results indicate that LV regional work can be assessed reliably from the T-A loop in both normal and regionally ischemic hearts. Regional work correlated linearly with end-diastolic regional area, indicating a regional Frank-Starling relation, and the slope of this relationship increased with dobutamine infusion and decreased with global ischemia. The correlation between regional work and LV stroke work was also linear and the regression line was the same during the control state and global ischemia, indicating a constant relationship between the work of a specific wall region and LV stroke work regardless of global changes in contractile state. However, after regional ischemia, this regression line apparently shifted downward because T-A loops in the ischemic region were extremely deformed and regional work markedly decreased. From these results, we conclude that T-A loops are a reliable and useful means of assessing regional contractile performance of the LV.

Animals↗
PubMed2002

Protective immune responses to the 42-kilodalton (kDa) region of Plasmodium yoelii merozoite surface protein 1 are induced by the C-terminal 19-kDa region but not by the adjacent 33-kDa region.

Vaccination of mice with the 42-kDa region of Plasmodium yoelii merozoite surface protein 1 (MSP1(42)) or its 19-kDa C-terminal processing product (MSP1(19)) can elicit protective antibody responses in mice. To investigate if the 33-kDa N-terminal fragment (MSP1(33)) of MSP1(42) also induces protection, the gene segment encoding MSP1(33) was expressed as a glutathione S-transferase (GST) fusion protein. C57BL/6 and BALB/c mice were immunized with GST-MSP1(33) and subsequently challenged with the lethal P. yoelii YM blood stage parasite. GST-MSP1(33) failed to induce protection, and all mice developed patent parasitemia at a level similar to that in naive or control (GST-immunized) mice; mice immunized with GST-MSP1(19) were protected, as has been shown previously. Specific prechallenge immunoglobulin G (IgG) antibody responses to MSP1 were analyzed by enzyme-linked immunosorbent assay and immunofluorescence. Despite being unprotected, several mice immunized with MSP1(33) had antibody titers (of all IgG subclasses) that were comparable to or higher than those in mice that were protected following immunization with MSP1(19). The finding that P. yoelii MSP1(33) elicits strong but nonprotective antibody responses may have implications for the design of vaccines for humans based on Plasmodium falciparum or Plasmodium vivax MSP1(42).

Animals↗
PubMed2005

[Implementation of State Policy in healthy nutrition of the population of the Russian Federation on the regional level: building-up regional policy and programs. Methodical aspects of development and implementation. Part 2. Recommendations were made development and realization of regional policy and programs in the healthy nutrition of the population].

Recommendations were made development and realization of regional policy and programs in the healthy nutrition of the population.

Food Supply↗
PubMed1986

Regional perfusion, glucose metabolism, and wall motion in patients with chronic electrocardiographic Q wave infarctions: evidence for persistence of viable tissue in some infarct regions by positron emission tomography.

Positron-emission tomography with 13N-ammonia and 18F-2-deoxyglucose was used to assess regional perfusion and glucose utilization in 31 chronic electrocardiographic Q wave regions in 20 patients. With previously published criteria, regions of infarction were identified by a concordant reduction in regional perfusion and glucose utilization, and regions of ischemia were identified by preservation of glucose utilization in regions of diminished perfusion. Only 10 of the 31 regions (32%) exhibited myocardial infarction tomographically. In contrast, positron tomography revealed ischemia in six regions (20%) and was normal in 15 regions (48%). Even when Q wave regions were reassigned and consolidated to enhance the specificity of the electrocardiogram, uptake of 18F-2-deoxyglucose was noted in the majority (54%) of the regions. Neither electrocardiographic ST-T changes nor severity of associated wall motion abnormality reliably distinguished tomographically identified regions of ischemia from infarction. Thus positron tomography reveals evidence of persistent tissue metabolism in a high proportion of chronic electrocardiographic Q wave regions, and commonly used clinical tests do not reliably distinguish hypoperfused but viable regions from tomographically defined regions of myocardial infarction.

Adult↗
PubMed1991

Sequencing of selected regions of the human immunoglobulin heavy-chain gene locus that completes the sequence from JH through the delta constant region.

Much of the nucleotide sequence between the start of the joining region and the end of the immunoglobulin heavy chain delta gene has already been determined. However, two gaps existed in potentially functionally important regions in this sequence: the region between the 3' end of the joining region and the heavy chain enhancer region and that between the enhancer and the mu constant region. We have determined the nucleotide sequences of these regions. The 734 bp between the joining and enhancer regions contained no additional joining regions. The 4525 bp region between the heavy chain enhancer and the mu constant region contains the mu switch region, which consists of pentameric repeats. Approximately 60% of these repeats are GGGCT and GAGCT. With the determination of these sequences, the entire region of the heavy chain locus starting upstream of the joining region to downstream of the last exon of the delta constant region (a total of more than 29 kb) has now been sequenced.

Base Sequence↗
PubMed1983

Local-regional treatment of patients with simultaneous local-regional recurrence and distant metastases following mastectomy.

High-dose, large volume local-regional irradiation has been shown to be necessary in patients with local-regional recurrence of breast cancer without coexisting distant metastases; however, no studies exist that deal with the dose and volume of local-regional irradiation required for patients with both local-regional recurrence and distant metastases. This report is an analysis of 68 patients who presented with previously untreated local-regional recurrence and coexisting distant metastases. Thirty-five of these patients were treated with local-regional irradiation and systemic therapy; the remaining 33 patients received systemic therapy only. An analysis of the dose and volume in the 35 irradiated patients showed that if the irradiation was inadequate (dose less than 4500 rad and volume not large enough to encompass the entire involved site), the incidence of uncontrolled local-regional disease for the duration of life was 79%, similar to the 64% rate of uncontrolled local-regional disease in the 33 patients not receiving local-regional irradiation. On the other hand, if the dose to the recurrence was at least 4500 rad and if the field was large enough to encompass the entire site containing the recurrence, the incidence of uncontrolled local-regional disease for the duration of life was only 27%. The present study also suggests that local-regional irradiation may be indicated in patients with asymptomatic as well as symptomatic local-regional disease. In patients with distant metastases and initially asymptomatic local-regional disease, adequate irradiation resulted in a lower incidence of ultimate local-regional symptoms when compared to similar patients who were treated with inadequate or no local-regional irradiation. This difference was not quite statistically significant because of the small number of patients in each group.

Breast Neoplasms↗
PubMed1988

Relationship between the relative regional thallium-201 uptake and the regional systolic or diastolic filling function.

Both the resting thallium-201 imaging and resting gated radionuclide ventriculography were conducted in the left anterior oblique view in 35 patients with isolated disease of the left anterior descending coronary artery (LAD), and the corresponding involved region was compared from two differing perspectives, one measuring regional ventricular function and the other regional myocardial perfusion. In the thallium-201 imaging, the thallium activity in the septal or apical region supplied by the LAD was calculated as an activity ratio between the mean value of the normally perfused lateral region and that of the septal or apical region, and was called relative thallium uptake (%T1 uptake). In the gated radionuclide ventriculographic study, a computer program subdivided the image of the left ventricle into 4 regions. The time-activity and first-derivative curves were computed in the septal and apical regions. Significant positive correlations were present between the %T1 uptake and the ejection fraction or peak ejection rate both in the septal and apical regions, indicating that the regional systolic function diminishes progressively as the perfusion abnormality increases. However, positive but poor and scattering correlations were found between the %T1 uptake and the peak filling rate, and there were no significant correlations between the %T1 uptake and the filling period in these affected regions. Thus, we could suppose that the regional systolic function is closely related to the regional %T1 uptake which probably reflects the amount of the residual viable myocardium, but there is the possibility that the regional diastolic filling function may be not so much related to the amount of the viable myocardium as is systolic function or may be modulated by some factors other than the amount of the regional viable myocardium.

Adult↗