Differentiating benign and malignant salivary gland tumours: diagnostic criteria and the accuracy of dynamic contrast-enhanced MRI with high temporal resolution.

OBJECTIVE: To determine the optimal diagnostic criterion of dynamic contrast-enhanced MRI (DCE-MRI) for predicting salivary gland malignancy using a dynamic sequence with high temporal resolution, as well as the accuracy of this technique. METHODS: The DCE-MRI findings of 98 salivary gland tumours (74 benign and 24 malignant) were reviewed. MR images were sequentially obtained at 5-s intervals for 370 s. Two parameters, peak time and washout ratio (WR) were determined from the time-signal intensity curve. The optimal thresholds of these parameters for differentiating benign and malignant tumours were determined, along with the diagnostic accuracy of the criterion using these thresholds. RESULTS: A peak time of 150 s and a WR of 30% were identified as optimal thresholds. As the criterion for malignancy, the combination of peak time <150 s and WR <30% provided a sensitivity of 79% (19/24), specificity of 95% (70/74) and an overall accuracy of 91% (89/98). Three of the five false-negative cases were malignant lymphomas of the parotid gland. CONCLUSION: Peak time <150 s with WR <30% comprised the optimal diagnostic criterion in predicting salivary gland malignancy, providing a sensitivity of 79% and specificity of 95%. The use of high temporal resolution might improve the accuracy of DCE-MRI. ADVANCES IN KNOWLEDGE: Although several studies have reported the usefulness of DCE-MRI in the differential diagnosis of salivary gland tumours, the specific diagnostic criteria employed have differed widely. We determined the optimal criterion and its accuracy using a dynamic sequence with high temporal resolution.

Effects of curcumin supplementation on exercise-induced oxidative stress in humans.

The purpose of this study was to investigate the effects of curcumin supplementation on exercise-induced oxidative stress in humans. 10 male participants, ages 26.8±2.0 years (mean±SE), completed 3 trials in a random order: (1) placebo (control), (2) single (only before exercise) and (3) double (before and immediately after exercise) curcumin supplementation trials. Each participant received oral administration of 90 mg of curcumin or the placebo 2h before exercise and immediately after exercise. Each participant walked or ran at 65% of V˙2max on a treadmill for 60min. Blood samples were collected pre-exercise, immediately after exercise and 2h after exercise. The concentrations of serum derivatives of reactive oxygen metabolites measured immediately after exercise were significantly higher than pre-exercise values in the placebo trial (308.8±12.9 U. CARR, P<0.05), but not in the single (259.9±17.1 U. CARR) or double (273.6±19.7 U. CARR) curcumin supplementation trials. Serum biological antioxidant potential concentrations measured immediately after exercise were significantly elevated in the single and double curcumin supplementation trials compared with pre-exercise values (P<0.05). These findings indicate that curcumin supplementation can attenuate exercise-induced oxidative stress by increasing blood antioxidant capacity.

Free jejunal diversionary conduit flaps following radiation damage to the pharynx: a technique for regaining oral feeding while preserving vocal function.

UNLABELLED: Radiotherapy is an accepted primary treatment modality for head and neck malignancies. However, in severe cases, the chronic radiation damage has resulted in dysphagia, aspiration and choking. Failure in conservative therapeutic strategies for this swallowing dysfunction will result in either preservation of voice with loss of oral feeding, or vice versa. We introduce our surgical technique based on the free jejunal diversionary conduit flaps, which helps patients to resume oral feeding and preserves vocal function, while reducing the risk of aspiration. METHOD: Six patients suffering from swallowing dysfunction following radiotherapy were enrolled. All were dependent on tube feeding. A subcutaneously transferred free jejunal flap connected the left buccogingival sulcus to the cervical oesophagus, which permanently separates the airway from the native aerodigestive tract by creating a new inlet for food passage. Simultaneously created pharyngostomy drains accumulation of saliva and food residue in the epiglottic vallecula and the pyriform sinus. For the cases with tight fibrotic neck skin, we divided this technique into two stages. RESULTS: All cases could take at least semi-solid food orally, with some minor complications in the initial four cases. Five cases were independent of tube feeding. Two recent cases with modifications did not experience any complication and could start oral intake much earlier (7 days after surgery) than previous cases (118 days on average). CONCLUSION: The free jejunal diversionary conduit flaps offer post-radiotherapy patients with swallowing dysfunction the option to resume oral feeding while preserving their voice and reducing the risk of aspiration.

Differentiation between superficial and deep lobe parotid tumors by magnetic resonance imaging: usefulness of the parotid duct criterion.

BACKGROUND: The location of a parotid tumor affects the choice of surgery, and there is a risk of damaging the facial nerve during surgery. Thus, differentiation between superficial and deep lobe parotid tumors is important for appropriate surgical planning. PURPOSE: To evaluate the usefulness of using the parotid duct, in addition to the retromandibular vein, for differentiating between superficial and deep lobe parotid tumors on MR images. MATERIAL AND METHODS: Magnetic resonance images of 42 parotid tumors in 40 patients were reviewed to determine whether the tumor was located in the superficial or deep lobe. In each case, the retromandibular vein and the parotid duct were used to locate the tumor. The parotid duct was only used in cases where the tumor and the duct were visualized on the same image. RESULTS: Using the retromandibular vein criterion, 71% of deep lobe and 86% of superficial lobe tumors were correctly diagnosed, providing an accuracy of 81%. However, the accuracy achieved when using the parotid duct criterion was 100%, although it could be applied to only 28 of the 42 cases. Based on these results, we defined the following diagnostic method: the parotid duct criterion is first applied, and for cases in which it cannot be applied, the retromandibular vein criterion is used. The accuracy of this method was 88%, which was better than that achieved using the retromandibular vein criterion alone. CONCLUSION: The parotid duct criterion is useful for determining the location of parotid tumors. Combining the parotid duct criterion with the retromandibular vein criterion might improve the diagnostic accuracy of parotid tumor location compared to using the latter criterion alone.

A potential pitfall of MR imaging for assessing mandibular invasion of squamous cell carcinoma in the oral cavity.

BACKGROUND AND PURPOSE: Whether MR imaging is superior to CT in evaluating the presence and extent of mandibular invasion by squamous cell carcinoma remains controversial. The purpose of this study was to directly compare the diagnostic accuracy of MR imaging and that of CT. METHODS: MR and CT images in 51 patients with squamous cell carcinoma of the oral cavity were evaluated for the presence and extent of mandibular invasion. The results were correlated with histopathologic findings. RESULTS: Twenty-five of 51 patients had histopathologic evidence of mandibular cortical invasion. The tumor involved both the cortex and the bone marrow in all 25 patients and involved the inferior alveolar canal in 5 patients. The sensitivity and specificity for mandibular cortical invasion were 96% and 54% for MR imaging and 100% and 88% for CT, respectively. Those for inferior alveolar canal involvement were 100% and 70% for MR imaging and 100% and 96% for CT, respectively. In both evaluations, the specificity of MR imaging was significantly lower than that of CT (McNemar test, P = .004 in the former and P = .002 in the latter). Chemical shift artifact by bone marrow fat was postulated to be the source of most false-positive cases on MR imaging findings for mandibular cortical invasion. Those for inferior alveolar canal involvement were due to MR imaging visualization of the tumor and surrounding inflammation with similar signal intensity. CONCLUSION: In assessing the presence and extent of mandibular invasion by squamous cell carcinoma, the specificity of MR imaging was significantly lower than that of CT.

Suppression of tumor necrosis factor-alpha by beta2-adrenoceptor activation: role of mitogen-activated protein kinases in renal mesangial cells.

OBJECTIVE: The present study examined the inhibitory effect of beta2-adrenoceptor activation on the mitogen-activated protein kinase (MAPK) cascades and the contribution of these pathways to the suppression of tumor necrosis factor (TNF)-alpha in lipopolysaccharide (LPS)-stimulated rat renal mesangial cells. MATERIALS AND METHODS: Experiments were performed using cultured mesangial cells in the presence of LPS (1 microg/ml) and/or the beta2-adrenoceptor agonist, terbutaline (10(-6) 10(-8) M). The levels of extracellular signal-regulated kinase-1 and 2(Erk 1/2), p38, c-Jun N-terminal protein kinase (JNK) and TNF-alpha were estimated. RESULTS: LPS activated Erk-1/2 and p38 levels, by 4.7-fold and 1.8-fold, respectively (P < 0.05), which were suppressed by terbutaline (10(-6) - 10(-8) M) in a dose dependent way. These inhibitory actions of terbutaline were prevented by the beta2-adrenoceptor antagonist, ICI 118,551(10(-6) M) but not by an inhibitor of the cAMP-PKA pathway, H-89 (5 x 10(-6) M). The selective MAPK/Erk-1 inhibitor, PD98059 (10(-5) M) and the specific p38 inhibitor SB203580 (10(-5) M) significantly decreased LPS-induced TNF-alpha production in the cells. CONCLUSIONS: Inhibition of MAPK cascades (Erkl/2 and p38) plays an important role in the suppression of TNF-alpha following beta2-adrenoceptor activation but the inhibitory effect on MAPK is independent of the cAMP-PKA pathway in the mesangial cell.

beta(2)-adrenoceptor agonist suppresses renal tumour necrosis factor and enhances interleukin-6 gene expression induced by endotoxin.

BACKGROUND: beta(2)-Adrenoceptor activation regulates tumour necrosis factor (TNF)-alpha and interleukin-6 (IL-6) production in cultured renal cells. However, it remains uncertain whether, in vivo, the administration of beta(2)-adrenoceptor agonists regulate renal TNF-alpha and IL-6 mRNA following lipopolysaccharide (LPS) stimulation to cause endotoxaemia. This study was performed in order to evaluate the effect of beta(2)-adrenoceptor agonist on renal TNF-alpha and IL-6 production. METHODS: Four-week-old Wistar rats pre-treated with the beta(2)-adrenoceptor agonist terbutaline or formoterol, and/or the beta- and beta(2)-adrenoceptor antagonists (propanolol, ICI118,551), were injected with LPS (1 mg i.p.), and then 2, 4 or 6 h later, kidneys (cortex, medulla), spleen, thymus and plasma were collected to assay TNF-alpha and IL-6 mRNA levels and their respective protein release. RESULTS: Administration of beta(2)-adrenoceptor agonists suppressed TNF-alpha mRNA expression in the whole kidney, by 61% (P<0.05), as well as plasma, spleen and thymus TNF-alpha protein and mRNA expression 2 hours after injection of LPS. On the other hand, although IL-6 levels in plasma, spleen and thymus mRNA expression were suppressed significantly by administration of beta(2)-adrenoceptor agonists, the basal- and LPS-induced IL-6 mRNA levels in the whole kidney were increased 1.6- and 1.2-fold (P<0.05), respectively, by treatment with beta(2)-adrenoceptor agonists. beta(2)-Adrenoceptor agonist suppressed LPS-induced TNF-alpha mRNA expression by 35% (P<0.05) and stimulated LPS-induced IL-6 mRNA expression by 1.5-fold (P<0.05) in the medullary region of kidney. CONCLUSIONS: beta(2)-Adrenoceptor agonists down-regulate renal TNF-alpha mRNA expression following LPS-induced endotoxaemia. This effect was particularly apparent in the renal medulla. IL-6 mRNA expression in the renal medulla was up-regulated by the agonists whereas plasma, spleen and thymus IL-6 levels were completely inhibited by the agonist, which suggests the existence of tissue specific regulation of IL-6 production in the kidney by beta(2)-adrenoceptor activation.

Beta2-adrenoceptor agonist suppresses tumour necrosis factor production in rat mesangial cells.

This study aimed to investigate the time-course of the effect of beta2-adrenoceptor stimulation with terbutaline on lipopolysaccharide (LPS)-induced tumour necrosis factor(TNF)-alpha production in rat mesangial cells. Cells were cultured from 0-24 h in the presence of LPS (1 microg/ml) and/or terbutaline (10(-7)-10(-8) mol/l). After 1 h of incubation, terbutaline inhibited TNF-alpha protein release as well as transcription and translation of TNF-alpha and mitogen activated protein kinase (MAPK, p42/p44) activity. At 3 h, terbutaline enhanced intracellular cAMP but suppressed TNF-alpha release and transcription. By 24 h, whereas terbutaline was no longer influencing transcription or translation, TNF-alpha release remained depressed which correlated with an increase in supernatant interleukin (IL)-6. Terbutaline did not affect the LPS-induced IL-10 produced in the cell. These findings indicate that beta2-adrenoceptor stimulation during an LPS challenge prevented TNF-alpha production as a consequence of MAPK inhibition and enhanced cAMP generation, which at a later stage was associated with an anti-inflammatory effect of IL-6.

Effect of beta(2)-adrenoceptor activation and angiotensin II on tumour necrosis factor and interleukin 6 gene transcription in the rat renal resident macrophage cells.

This study aimed to examine whether lipopolysaccharide (LPS)-induced increase in tumour necrosis factor alpha (TNF-alpha) and interleukin 6 (IL-6) gene transcription was regulated by beta-adrenoceptor activation and whether TNF-alpha and IL-6 gene transcription was regulated by angiotensin II in rat renal resident macrophage cells. The cells were transfected with a fusion gene with the 5'-flanking region of rat TNF-alpha or IL-6 genes linked to a luciferase coding sequence as a reporter. The stimulatory effect of LPS on TNF-alpha transcription was suppressed by isoproterenol (10(-8)-10(-5)M) in a dose-dependent manner, whereas IL-6 transcription was only decreased by the high concentration (10(-5)M) of isoproterenol. The addition of beta(2)-adrenoceptor antagonist (ICI118,551), but not a beta(1)-adrenoceptor antagonist (atenolol), blocked the inhibitory effect of isoproterenol. By contrast, angiotensin II (10(-8)-10(-5)M) enhanced IL-6 gene transcription in the cells in a dose-dependent manner which was inhibited by type 1 angiotensin II receptor antagonist (CV11,974). TNF-alpha and IL-6 secretion from the cells was altered with beta(2)-adrenoceptor agonists (terbutaline, formoterol) and angiotensin II corresponding to changes of TNF-alpha and IL-6 gene transcription. Angiotensin II had no effect on TNF-alpha secretion and gene transcription. These findings suggested that beta(2)-adrenoceptor agonist and angiotensin II potentially could influence renal immune function through the regulation of TNF-alpha and IL-6 gene transcription by the renal resident macrophage cells.

Modulation of interleukin-6 by beta2-adrenoceptor in endotoxin-stimulated renal macrophage cells.

BACKGROUND: Activation of the cAMP signaling pathway by means of beta2-adrenoceptor agonists has been shown to up-regulate interleukin-6 (IL-6) gene expression and to stimulate IL-6 production in macrophage cells. However, whether beta2-adrenoceptor activation can also modify the rate of IL-6 production in macrophage cells activated by the bacterial endotoxins has not yet been determined. Using renal resident macrophage cells treated with endotoxin, lipopolysaccharide (LPS), and beta2-adrenoceptor agonist, terbutaline, we investigated the role of cAMP pathway, tumor necrosis factor (TNF)-alpha and mitogen-activated protein kinase (MAPK) pathway (p42/p44) in regulating IL-6 production. METHODS: IL-6 protein, mRNA, and promoter activity were measured in these cells exposed to LPS (1 microg/ml) and/or terbutaline (10(-9) to 10(-6) M). Furthermore, the time course effects of terbutaline on cAMP, MAPK (p42/p44), and TNF-alpha release were evaluated in the cells. RESULTS: Terbutaline at high concentrations (10(-6) M) significantly up-regulated IL-6 by approximately 25% (P<0.05), whereas at a lower concentration (10(-8) M), it down-regulated IL-6 production by 42% (P<0.05). Terbutaline (10(-8) and 10(-6) M) caused a concentration- and time-dependent stimulation of cAMP (P<0.05) and TNF production (P<0.05) and a time-dependent decrease in MAPK activity (P<0.05). Following the addition of a cAMP inhibitor, IL-6 promoter activity was correlated with TNF-alpha levels and MAPK activity. CONCLUSIONS: A biphasic effect of beta2-adrenoceptor agonist on IL-6 production in renal resident macrophage cells became apparent when LPS was exposed to the cells. The terbutaline-induced down-regulation of IL-6 gene production was mediated by an inhibitory effect of terbutaline on TNF-alpha, which was exerted through the MAPK and cAMP pathways, whereas the up-regulation appeared to be due to a direct action of intracellular cAMP.

Regulation of tumour necrosis factor and interleukin-6 gene transcription by beta2-adrenoceptor in the rat astrocytes.

The present study was designed to clarify the role of beta2-adrenoceptors in modulating the level of TNF and IL-6 gene transcription and their respective mRNA accumulations. Astrocytes were transfected with the 5'-flanking region of the TNF and IL-6 genes linked to a luciferase coding sequence as a reporter. The addition of isoproterenol had an inhibitory effect on the TNF and IL-6 promoter activity induced by LPS. The inhibitory effect was blocked in the presence of a beta2-adrenoceptor antagonist but not in the presence of a beta1-adrenoceptor antagonist. TNF and IL-6 mRNA and protein levels in the astrocytes were depressed by beta2-adrenoceptor activation which corresponded to changes in TNF and IL-6 promoter activity. These studies demonstrated that isoproterenol, via beta2-adrenoceptors, suppressed LPS-induced TNF and IL-6 promoter activities, mRNA accumulations, and protein levels in the astrocytes. Beta2-adrenoceptor activation may be an important mechanism for regulating TNF and IL-6 expression in brain diseases.

Efficient production of the C-terminal domain of secretory leukoprotease inhibitor as a thrombin-cleavable fusion protein in Escherichia coli.

We have developed a high-level production system for the C-terminal domain of secretory leukoprotease inhibitor (SLPI) to investigate its pharmacological activities. A gene for the C-terminal domain of SLPI, (Asn55-Ala 107)SLPI, was constructed from chemically synthesized deoxyoligonucleotides. It was fused to a gene for the N-terminal portion of human growth hormone via a DNA sequence encoding Leu-Val-Pro-Arg, which can be cleaved by thrombin. The fused gene was expressed in Escherichia coli under the control of a trp promoter, and the fusion protein was obtained as an inclusion body. After sulfonation of the cysteine residues, the sulfonated fusion protein was cleaved at the desired site by thrombin. Sulfonated (Asn55-Ala107) SLPI was refolded in Tris buffer containing reduced and oxidized glutathione. The resulting (Asn55-Ala107) SLPI was purified by cation-exchange chromatography and reverse-phase high performance liquid chromatography. The final yield was 50 mg/I culture. (Asn55-Ala107) SLPI was as active against elastase as, but had less trypsin inhibitory activity than, native SLPI. This system is suitable for the large-scale production of the C-terminal domain of SLPI, which is an elastase-specific inhibitor.

Reproducible procedures for establishing mouse thymic stromal cell lines.

Mouse thymic epithelial cell lines (MTEC) were established from Day 14-18 fetal thymus by two novel protocols. The first protocol involved the selection of TEC by the formation of complexes with adult thymocytes after transformation with the helper-free Ad5.SVR4 recombinant virus. The second protocol involved the stimulation and selection of TEC in Ca(2+)-free medium by the formation of complexes with Day 14 fetal thymocytes. The resulting TECs formed several types of thymic epithelial clusters to which Day 14 fetal thymocytes could bind. Many of these fetal thymocytes could deeply infiltrate, colonize, and proliferate within the clusters of NCAM(high) LFA-1(low) TEC (MTSC-0420-1.4, MTSC-0420-1.5, and MTSC-0613-1.2 clusters), whereas very few could infiltrate the clusters of NCAM(low) LFA-1(high) TEC (MTSC-0531-5.1 and MTSC-0531-5.2) and none bound to or infiltrated an NCAM(neg) fibroblast cluster (MTSC-fibro.). Hence, it is possible that the NCAM-positive epithelial cell lines are derived from the thymus cortex, where they may play an important role in intrathymic migration and the clonal growth of pro-T cells in fetal thymus.

Guinea-pig treatment with pertussis toxin suppresses macrophage-dependent bronchoconstriction by fMLP and fails to inhibit the effects of PAF.

1. Bronchoconstriction and thromboxane B2 (TxB2) release following the intra-tracheal administration of the secretagogue N-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLP) to lungs from pertussis toxin-treated guinea-pigs in vivo and in vitro were inhibited as compared to saline-treated animals, under conditions where the responses to PAF were modified less effectively. 2. The cell target accounting for bronchoconstriction by fMLP and for inhibition by pertussis toxin is located in the airways and is probably the alveolar macrophage. Indeed (a) fMLP-induced superoxide anions and TxB2 formation by alveolar macrophages were inhibited by pertussis toxin given in vivo; (b) Gi proteins of membranes from alveolar macrophages were ADP-ribosylated in vivo by pertussis toxin and (c) bronchoconstriction and TxB2 release in response to the intra-tracheal administration of fMLP to lungs from pertussis toxin-treated animals were restored when alveolar macrophages from control guinea-pigs were transferred into the airways of pertussis toxin-treated animals before lung isolation. 3. Pertussis toxin administered to guinea-pigs in vivo, reduced the subsequent TxB2 formation and superoxide anion release by alveolar macrophages stimulated with PAF, but failed to inhibit PAF-induced bronchoconstriction. 4. Formation of TxB2 by alveolar macrophages following the intra-tracheal administration of fMLP accounts for bronchoconstriction and requires pertussis toxin-sensitive Gi proteins. PAF operates via a different mechanism, which is independent of Gi-like protein and involves mediators other than TxB2 and superoxide anions.

Serum secretory leukoprotease inhibitor levels to diagnose pneumonia in the elderly.

In pneumonia in the elderly, one occasionally encounters difficulties in evaluation with respect to both clinical observation and treatment. Thus a simple serum indicator is indicated. We measured secretory leukoprotease inhibitor (SLPI) concentrations in sera to see whether this can provide a useful indicator for pneumonia, especially in the elderly. Serum samples from patients over 65 yr of age, with (n = 54) or without (n = 87) pneumonia, and from healthy, young (n = 16) and aged (n = 188) control subjects were assayed using ELISA for human SLPI. Comparisons were made between groups with clinical diagnoses of either definite or probable pneumonia and among cases with various other respiratory diseases, including bronchial asthma, chronic obstructive pulmonary disease, and lung cancer. The mean SLPI concentration in patients with pneumonia was significantly higher than in patients without pneumonia or in healthy controls. The data suggest that the measurement of SLPI can provide a useful indicator for pneumonia to be used in clinical evaluation.

Sustained release of 5-fluorouracil from oil/water emulsions.

Release profile of 5-fluorouracil (5-FU) from O/W emulsion and bone marrow toxicity of 5-FU to mice were compared with those of an aqueous solution of 5-FU. 5-FU emulsion had lower bone marrow toxicity and a slower drug release rate than the 5-FU aqueous solution which exhibited high bone marrow toxicity and fast drug release rate. A correlation between the rate of drug release and bone marrow toxicity was suggested.

Migration of putative progenitor T cells in response to thymus-derived chemotactic factors.

Progenitor T cells reach the thymus through the circulation from hematopoietic organs and then migrate toward the site of differentiation in the thymus. The mechanism that regulates such intrathymic migration is not well understood. In order to clarify this mechanism, in vitro chemotactic activity for murine thymocytes was assayed in the extracts and culture supernatants of thymic tissue elements. A potent thymocyte chemotactic activity was found in the extract and culture supernatant from Ig-, Ia- thymic stromal cells. Peanut agglutinin-positive (PNA+1), Thy 1+, TL-, Lyt 1+2-, L3T4- thymocytes, Ig-, Thy 1- bone marrow cells, and mononuclear cells of spleen and peripheral blood, but neither B cells nor lymph node cells, were chemotactically attracted by the factor(s). The chemotactic activity was found in none of the following materials tested: the extract and culture supernatant of thymocytes, culture supernatant of lymph node stromal cells, normal mouse serum, and zymosan-activated serum. The chemotactic activity was found in three molecular fractions by gel chromatography. The activity in all three fractions was destroyed by trypsin digestion or by heating at 56 degrees C for 30 min. These results suggest that Ig-, Ia- thymic stromal cells but not thymocytes secrete a chemotactic factor(s) for progenitor T cells with three molecular species. The factor is considered to play an important role in the migration of intrathymic progenitor T cells into the site of differentiation.

Monoclonal anti-Thy-1.2 antibody induced hematopoiesis in vivo.

The intravenous injection of a monoclonal anti-Thy-1.2 alloantibody (IgM class) induced a rapid increase in the number, and the ratio, of multipotent hematopoietic stem cells (CFU-S) in S-phase. The onset of hematopoiesis was thymus-independent. Reconstitution of lethally-irradiated mice with bone marrow cells from mice injected with antibody augmented the T-cell responsiveness to mitogens. No activation was observed in granulocyte/macrophage progenitors. The monoclonal antibody did not directly stimulate CFU-S in vitro, although hematopoietic activity could be found in the sera of antibody-injected mice. Immediately after injection, the antibody was found bound on Thy-1+ cells in spleen. No decrease in the number of peripheral T cells was seen. These results seem to indicate that Thy-1.2-positive cells bound with anti-Thy-1.2 alloantibody may secrete a factor which induces the proliferation of hematopoietic stem cells.

A chemotactic factor for rat thymocytes may regulate T-lymphocyte migration toward the thymic microenvironment.

Using a modified Boyden chamber assay, extracts or culture supernatants of rat thymic stromal cells, or thymocytes were examined by chemotactic activity to rat leukocytes. Rat thymocytes responded chemotactically to the aqueous extract as well as to culture supernatants of thymic stromal cells. However, neither the extract and culture medium from concanavalin A-stimulated thymocytes nor any component of rat serum has shown such an activity. The thymic extract was fractionated into three molecular species with chemotactic activity for thymocytes. The thymocyte chemotactic factor(s) (TCFs) in the extract was distinct from known lymphocytic chemotactic factors, such as interleukin-1 (IL-1), IL-2, C5a, and the culture supernatant of stimulated thymocytes. In vitro, TCFs could attract, in addition to thymocytes, bone marrow cells, fetal liver cells, and nylon-wool nonadherent lymphocytes from peripheral blood and spleen. Lymph node cells, neutrophils, macrophages, and B cells from peripheral blood could not respond to TCFs. Thymocytes also responded to the extract of splenic stromal cells. Unlike the thymic extract, however, the splenic extract was chemotactically active for lymphocytes from lymph nodes but not for bone marrow cells. These results indicate that thymic stromal cells secrete a chemotactic factor(s) for a relatively immature type of T-lineage cells, which may by a thymus-homing progenitor T cell, while spleen may contain an attractant for a relatively mature type of T-lineage cells.

[Synergistic action of lentinan (LNT) with endocrine therapy of breast cancer in rats and humans].

With the aim of clarifying the nature of the synergistic action of LNT with endocrine therapy for mammary tumor, the effect of LNT post-treatment was investigated in rats with DMBA-induced mammary tumors and also in patients with recurrent breast cancer. LNT injection following surgical therapy (Ax + Ox) resulted in a much greater regression of tumor growth than that obtained by surgery alone, but not after medical therapy (Tamoxifen). Image analysis using an immunohistochemical technique revealed that LNT-surgical therapy resulted in marked atrophy of tumors and as well as intense infiltration of T cells, B cells and macrophages into the stroma around the tumor. Blood prolactin level was greatly reduced by LNT injection. A clinical randomized controlled study demonstrated the efficacy and safety of LNT post-treatment with surgical therapy in 33 patients with recurrent breast cancer. The mode of the synergistic action of LNT in combination with endocrine therapy on hormone-dependent tumors was discussed.