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In normal hematopoiesis, granulocyte macrophage-colony stimulating factor (GM-CSF) is known to stimulate the proliferation and differentiation of myelo-monocytoid lineage, while Steel factor (SLF) has been supposed to support the proliferation of more primitive hematopoietic progenitors including stem cells. We investigated the stimulatory effect of SLF and GM-CSF in twelve cases of acute myeloid leukemia (AML) cells in vitro by MTT assay. In 10 out of 12 cases, SLF or GM-CSF stimulated the proliferation of leukemic cells in short term liquid culture. In 7 out of these 10 cases, the leukemic cells responded to both cytokines. To investigate the possibility of the clinical application of these cytokines by combination with cell cycle-specific anti-tumor reagents, we assessed the effects of SLF and GM-CSF on the modulation of the cell cycle and sensitivity against cytosine arabinoside (ara-C) in a human factor-dependent leukemic cell line, MO7e. Flow cytometric analysis revealed the effect of cell recruitment into the cell cycle in the quiescent MO7e cells by exposure to these cytokines. The drug-sensitivity test using the MTT assay system demonstrated that pre-treatment with each cytokine enhanced sensitivity of ara-C. Furthermore, by combination of SLF and GM-CSF, the ara-C sensitivity was significantly wore graty enhanced than by each cytokine alone. These data suggest that combined pre-treatment with SLF and GM-CSF may provide new benefits for cure-oriented chemotherapy of AML followed by bone marrow transplantation or peripheral blood stem cell transplantation.

According to WHO criteria in 1978, borderline hypertension is defined as systolic blood pressure between 140 and 159 mmHg and/or diastolic blood pressure between 90 and 94 mmHg. Compared with direct intravascular pressure measurement, values obtained by the conventional cuff method were 2 mmHg lower in systolic pressure and 2 mmHg higher in diastolic pressure. The precision of the cuff method was approximately +/- 4 mmHg in both systolic and diastolic pressures. In 20 patients with mild hypertension, arterial pressure fluctuated with respiration within ranges from 6 to 32 mmHg in systole and from 3 to 14 mmHg in diastole. From these results, repetitive blood pressure measurements are recommended for the diagnosis of borderline hypertension. Borderline hypertension is the most sensitive predictor of definite hypertension in the future. Long term follow up should be stressed.

Hepatocyte growth factor (HGF) is a potent mitogen for parenchymal liver cells, epithelial cells, and endothelial cells and may play an important role in liver regeneration following hepatic injury. HGF is homologous to plasminogen and is first synthesized and secreted as an inactive single-chain precursor and then activated to a heterodimeric form by endoproteolytic processing. Recently, a novel serine protease responsible for this processing (HGF activator) has been purified from fetal bovine serum (Shimomura, T., Ochiai, M., Kondo, J., and Morimoto, Y. (1992) Cytotechnology 8, 219-229). In this study, we purified HGF activator from human serum and determined its partial amino acid sequence. Based on the amino acid sequence, we have molecularly cloned the cDNA for human HGF activator. The nucleotide sequence of the cDNA revealed that HGF activator is derived from the COOH-terminal half region of a precursor protein of 655 amino acids and that the precursor consists of multiple putative domains homologous to those observed in blood coagulation factor XII. These domains may be involved in the conversion of the precursor to the active form of HGF activator.

A case of contralateral adrenal metastasis of renal cell carcinoma is reported. The patient was a 54-year-old male, who underwent a right radical transperitoneal nephrectomy for renal cell carcinoma, and had been administered interferon alpha intramuscularly. Nine months after the operation computerized tomography revealed the presence of an adrenal mass on the left side, undetected at nephrectomy, which suggested that the renal cell carcinoma had metastasized. A left adrenalectomy was performed. Histologically, the mass was identical to metastasis of renal cell carcinoma. The patient was administered supplementary hydrocortisone and was well 3 months after the adrenalectomy with no evidence of recurrence or other metastasis. This is the 24th case of contralateral adrenal metastasis of renal cell carcinoma in the Japanese literature.

Molecular cloning and characterization of cDNAs and genomic DNA for human HGF-SF revealed the expression pattern of the gene. Alternative use of splicing sites and processing/polyadenylation sites generates multiple mRNAs for human HGF-SF in a variety of tissues and cell lines. This alternative mRNA production may be regulated in a tissue-specific manner. Full-length HGF-SF is encoded by the 6.3 kb or 3.1 kb mRNA. A variant form of HGF-SF is encoded by the 1.5 kb mRNA which is generated by alternative splicing accompanied by the utilization of an alternative processing/polyadenylation site in an extra exon. The variant form consists of an N-terminal sequence and the first two kringles and acts as an antagonist of HGF-SF mitogenic activity. HGF-SF with a deletion of 5 amino acids in the first kringle is produced from an alternatively spliced mRNA. The deletion induces the change in the heparin-binding property of the protein. Analysis of responses of the HGF-SF mRNA during liver regeneration revealed that the HGF-SF gene is activated. The level of mRNA markedly increases in the rat liver, spleen and lung after administration of hepatotoxins. Characteristic regulatory elements, an IL6 response element and an NF-IL6 binding element, are present proximal to the major transcription initiation site in the human HGF-SF gene. These elements may be involved in the activation of the gene after liver injury. The potential autocrine role of HGF-SF in the acquisition of altered phenotypes was determined by introduction of the gene into target cells for HGF-SF. Autocrine production of the factor induces changes in cell properties from parental types to those obtained by the addition of exogenous factor.

During the past 30 years, a number of growth factors have been isolated and characterized. These include insulin and insulin-like growth factors, the fibroblast growth factors, the hematopoietic colony-stimulating growth factors, and the epidermal growth factor (EGF) group. Epidermal growth factor, which stimulates the growth of a variety of tissues, has been extensively studied since its discovery in the early 1960s. This review presents an historic perspective, basic scientific aspects, laboratory methods, and the clinical application of EGF in the specialty of obstetrics and gynecology. Expanding research on this factor together with its increasing clinical applications will undoubtedly predict its routine use in clinical practice. Understanding basic and applied knowledge of EGF will become essential for clinicians in adapting this new technology to patient care.

Fullerene nanowhiskers (FNWs) were synthesized by the liquid-liquid interfacial precipitation method and the adsorption properties of their heat-treated samples were characterized. It was found that vacuum-annealed FNWs at a high temperature are of microporous materials and, especially, ultramicropores are highly developed in these materials. Porosities even remain in samples after heat treatment at a temperature higher than 2273 K. The presence of ultramicroporosity is indicative of the molecular sieving properties of the vacuum-annealed FNW materials, suggesting the possibilities of their application as new materials for gas separation and gas storage.

The growth mechanism of C60 nanowhiskers (C60NWs) is investigated. The C60NWs were prepared by the liquid-liquid interfacial precipitation method (LLIP method). The length growth of C60NWs was investigated for various volume ratios between C60-saturated toluene solution and isopropyl alcohol. The length growth of C60NWs varied depending on the volume ratio. The optimum volume ratio in preparing C60NWs with a high uniformity was found to be 1:1. The water contained in isopropyl alcohol markedly influence the length growth of C60NWs. C60NWs did not form when isopropyl alcohol containing more than 2.5 mass % water was used.

Mouse strains carrying mutations at the Dominant White Spotting (W) locus or the Steel (Sl) locus are anemic and display defects in pigmentation and gametogenesis. In W mutants the anemia is due to a deficiency of hemopoietic stem cells and, in Sl mutants, to a deficiency of supporting stromal cells in the bone marrow. The W locus encodes the c-kit proto-oncogene product, a cell surface receptor with protein-tyrosine kinase activity, and the Sl locus encodes its ligand, a hemopoietic cytokine known variously as Steel factor (SLF), mast cell growth factor, stem cell factor, and Kit ligand. SLF can synergize with a number of other cytokines to stimulate growth of hemopoietic progenitors in vitro and stimulates blood cell production in vivo in animals. Here we review the biological activities of SLF, with particular emphasis on its effects on hemopoietic stem and progenitor cells. We also discuss present knowledge of the molecules involved in SLF-triggered signal transduction, and speculate on potential therapeutic applications for SLF in human disease.

Mast cell growth factor (MGF, the ligand for c-kit receptor) can stimulate proliferation of factor dependent myeloid cell line, M07e, and MGF synergizes with granulocyte-macrophage colony-stimulating factor (GM-CSF) or IL-3 in this effect. The effect of MGF on protein tyrosine kinase activity in M07e cells was investigated by immunoblotting with anti-phosphotyrosine mAb and this was compared with effects of GM-CSF. MGF stimulation rapidly induced or enhanced at least 12 tyrosine phosphorylated bands. Major bands had molecular weights of 145, 120, 110, 98, 62, 55 and 42 kD. P145, the most prominent phosphorylated protein, was identified as c-kit product using anti-c-kit-mAb (YB5.B8), suggesting ligand-dependent receptor autophosphorylation. Five of six tyrosine phosphorylated bands induced or enhanced by GM-CSF stimulation comigrated with those tyrosine phosphorylated by MGF (138, 120, 76, 55 and 42 kD). P42 was identified, at least in part, as mitogen-activated protein (MAP) kinase. MGF induced tyrosine phosphorylation of a complex of GTPase-activating protein (GAP, 120 kD) and GAP associated proteins (p62/p190) as detected by anti-GAP Ab immunoprecipitation followed by immunoblotting with anti-phosphotyrosine mAb. GM-CSF also stimulated slightly but consistently tyrosine phosphorylation of GAP and p190 but not p62. Both MGF and GM-CSF enhanced Raf-1 phosphorylation and increased Raf-1 associated kinase activity in vitro. Phosphoamino acid analysis revealed Raf-1 phosphorylation by these two growth factors occurred almost exclusively on serine residues. No tyrosine phosphorylation of Raf-1 protein was detected. These data suggest shared and unshared components of signaling pathways of both factors, which may be involved in cell proliferation.

Murine mast cell growth factor (muMGF), a c-kit ligand, has additive to greater-than-additive effects on in vitro colony formation of murine and human myeloid progenitor cells stimulated with erythropoietin, granulocyte-macrophage colony-stimulating factor (GM-CSF), and/or interleukin (IL)-3. To confirm direct-acting effects on responding cells, MGF was assessed alone and in combination with other cytokines for effects on the proliferation of the human factor-dependent cell line, M07e. Proliferation was assayed in liquid culture by [3H]thymidine uptake and in semisolid medium by colony formation. Purified recombinant (r) muMGF (25-50 ng/ml) by itself had proliferative activity but less than r human (hu) GM-CSF. In combination with rhuGM-CSF (250 U/ml) or IL-3 (500 U/ml), rmuMGF (25 ng/ml) enhanced [3H]thymidine uptake two- to sevenfold greater than the sum of the effects of each factor alone. Similar enhancement was seen in the number and size of colonies formed. When MGF was used in combination with rhuIL-4 (500-1000 U/ml), rhuIL-6 (5 ng/ml), rhuIL-9 (5-10 U/ml), or rhu interferon gamma (IFN-gamma; 250-500 U/ml) (factors that alone stimulate little proliferation), [3H]thymidine uptake and colony formation were respectively increased 2- to 11- and 3- to 55-fold over the sum of each of the effects of the factors alone. Exposure of 5 x 10(5) cells/ml to 50 ng/ml MGF for 24 h, a time during which synergism is noted with MGF plus either GM-CSF or IL-3, did not change GM-CSF or IL-3 receptor binding affinity or the number of binding sites. Exposure of cells to MGF for 48 h did not alter subsequent GM-CSF- or IL-3-stimulated proliferation. The results suggest that M07e cells will be useful as a model for the analysis of intracellular biochemical mechanisms of the direct-acting proliferative and synergistic effects of MGF.

The formation, growth and aggregation of calcium oxalate crystals were evaluated with a Coulter counter. CG-120 and sodium pentosan polysulfate (SPP) has inhibitory activity on calcium oxalate crystal formation, growth and aggregation in the seeded crystal system and whole urine system. In continuous crystallizer system, they inhibit the nucleation rate. A new system of observing the crystal formation and growth of fragmented stones after extracorporeal shock wave lithotripsy has been developed. CG-120 has an inhibitory effect on their growth. The deposition of calcium oxalate crystals in the rat kidney was induced, and the, the volume and number of crystals were estimated using a Coulter counter. SPP has an inhibitory effect on calcium oxalate crystal growth in vivo.

Between 1982 and 1990, 20 patients with chronic renal failure underwent total para-thyroidectomies and autotransplantations as treatment for secondary hyperparathyroidism. Fourteen cases were cured of their symptoms and their serum PTH levels was restored to normal. Recurrent hyperparathyroidism developed in 6 cases. In 3 of the 6 cases, excision of parathyroid tissue from the forearm could easily be performed under local anesthesia. Of the other cases, 2 had five and one had six glands. Several localizing methods should be performed before operation, in order to overlook the parathyroid glands in different anatomic positions.

Using a high definition television (HDTV) technique, we have designed and developed the real time microscopic image transmission system. The department of laboratory and pathology, 500 m apart, are connected by this system on a light fiber line. It consists of an electrically controlled microscope, a HDTV camera, a HDTV color monitor, and a video transmitter on the laboratory side, while on the pathology a remote microscope controller, a video receiver, and a HDTV color monitor of 22.5 (H)-39.5(W) cm in CRT size. By monitoring real time noiseless picture, pathologists can select the objective lenses, move the stage, and adjust the focus of microscope at their own office. Three-month trial revealed that this prototype system was quite useful for prompt histo-pathological diagnosis during surgical operations. So far as we know, this microscopic image transmission system with Hi-vision TV is the first one in practical use in this field.

In order to examine the aging effects on blood biochemical parameters, 25 aged females (70 +/- 8 years old at the beginning of this investigation) were studied prospectively for 7 years. Biochemical parameters were measured in 1982, 1985, 1987, and 1989. Component scores were obtained by principal component analysis applied to all of these 100 data. The data of 13 biochemical parameters and 4 component scores were analyzed for aging, cohort, and time effects by utilizing 3 types of approach i.e., longitudinal, cross-sectional, and time-series. Positive aging effects were observed on blood urea nitrogen and 4th component score. Fourth component score had positive relations to blood urea nitrogen and total bilirubin, and a negative relation to total protein. This 4th component score increased with longitudinal age changes among all cohorts divided by decade, and it increased markedly over 70 years old. These results suggest that the aging effects on biochemical parameters are related with both the decrease in glomerular and hepatocellular functions and the increase in breakdown of tissue protein.

Mice infected with the polycythemia-inducing strain of the Friend virus complex (FVC-P) have been used as a leukemic mouse model. In the present study, purified iron-saturated human lactoferrin (LF) and recombinant murine (rmu) interferon-gamma (IFN-gamma), alone or in combination, were used to influence disease progression in virally infected mice. DBA/2 mice were injected i.v. with FVC-P, and were treated s.c. with 100 micrograms LF at day 7, and/or rmuIFN-gamma at 5 x 10(4) units/day for 3 days beginning at day 6 after viral infection. Mice were assessed for survival, and also 14 days after virus inoculation, the mice were killed and spleen extracts were assessed for spleen focus forming virus (SFFV) titers by spleen focus forming unit (SFFU) assay, SFFV mRNA and genomic DNA expression, and natural killer (NK) cell activity. Treatment with LF or rmuIFN-gamma alone had little or no effect on SFFU numbers or SFFV mRNA or genomic DNA expression. However, dramatically decreased SFFV titers and levels of SFFV mRNA and genomic DNA were observed in mice treated with the combination of LF and rmuIFN-gamma. NK cell activity decreased by FVC-P was returned to normal levels by LF and rmuIFN-gamma. The combined treatment also enhanced the survival rates of FVC-P-infected mice. The results suggest synergistic suppressive effects of LF with rmuIFN-gamma on disease progression in FVC-P-infected mice. This information might be of significance as a potential therapy for patients with leukemia and those infected with retroviruses.

A direct-indirect hybrid implosion mode is proposed and discussed in heavy ion beam (HIB) inertial confinement fusion (HIF) in order to release sufficient fusion energy in a robust manner. On the other hand, the HIB illumination non-uniformity depends strongly on a target displacement dz from the centre of a fusion reactor chamber. In a direct-driven implosion mode, dz of ~ 20 μm was tolerable, and in an indirect-implosion mode, dz of ~ 100 μm was allowable. In the direct-indirect mixture mode target, a low-density foam layer is inserted, and the radiation energy is confined in the foam layer. In the foam layer the radiation transport is expected to smooth the HIB illumination non-uniformity in the lateral direction. Two-dimensional implosion simulations are performed, and show that the HIB illumination non-uniformity is well smoothed in the direct-indirect hybrid-mode target. Our simulation results present that a large pellet displacement of ~ a few hundred μm is allowed in order to obtain a sufficient fusion energy output in HIF.

The widespread use of serum human chorionic gonadotropin (hCG) monitoring has enabled earlier diagnosis of ectopic pregnancy and increasingly conservative methods of management including operative laparoscopy, medical therapy with methotrexate, and expectant management. We investigated the use of a combined laparoscopic and minilaparotomy approach as an operative management of ectopic pregnancy. Fifteen of 16 patients presenting to the Reproductive Endocrinology Service were managed using either operative laparoscopy or minilaparotomy. Serum hCG values at the time of diagnosis ranged from 239 to 8060 mIU/ml. Nine patients were managed by operative laparoscopy and six by minilaparotomy. All patients were ambulatory and tolerating oral intake within 8 hours of surgery. The average hospitalization was 31 hours from the time of surgery. Thirty-five percent of the patients were discharged within 24 hours and an additional 40% within 36 hours. This approach was applicable to all patients regardless of body habitus, degree of hemoperitoneum, or status of the ectopic pregnancy. Such a combined approach permitted minimal tissue manipulation and shortened hospitalization. Data of the present study suggest that such an approach may be applicable to most clinical circumstances, performed without undue morbidity and potentially avoid a standard laparotomy and its attendant risks and hospitalization.

Premature ovarian failure, diagnosed from elevated serum gonadotropin concentrations, is generally considered irreversible. That there have been isolated cases of pregnancy, however, suggests that ovarian function may persist in these patients. We recently studied the longitudinal progress of two patients with intermittent ovarian failure who manifested a spontaneous return of ovarian function and, in one patient, pregnancy.

The localization of creatine kinase M (CK-M) in both normal and acute ischemic canine myocardial cells was studied by immunoelectron microscopy using the anti-CK-M Fab'-horseradish peroxidase conjugate. Myocardial ischemia was induced by occlusion of the left anterior descending coronary artery for 15, 60, or 180 minutes. In the normal myocardial cells, CK-M was localized mostly in the A-band and some in the Z-line, M-line, sarcolemmal membrane, and membrane of sarcoplasmic reticulum. Most CK-M in the A-band appeared to associate with thick fibers. This finding strongly suggests that the CK associated with thick fibers may be the enzyme to rephosphorylate ADP produced by myosin ATPase. In 15 minutes of myocardial ischemia, CK-M showed only minimal changes in its location, i.e., almost similar to normal, indicating that the CK in the A-band still has the ability to couple with myosin ATPase. However, in 60 and 180 minutes of ischemia, the A-band CK dissociated markedly from thick fibers, diffused to the I-band and leaked out to the intercellular spaces. These results suggest that the dissociation and disappearance of the A-band CK from thick fibers induced by progress of myocardial ischemia disrupt the myocardial energy transport system via CK reaction, and lead to the irreversible injury of myocardial cells.

We report a case of malignant histiocytosis diagnosed by liver-spleen biopsy under laparoscopy. A 49-year-old woman was admitted to our hospital with thrombocytopenia, moderate anemia and hypoproteinemia. Her bone marrow findings revealed erythroid and megakaryocyte hyperplasia, and the serum ferritin concentration was 2,250 ng/ml though she had not received any blood transfusions. Ferrokinetics analysis showed the pattern of ineffective erythropoiesis, and the half-lives of erythrocytes and platelets were both shortened. Her hepatosplenomegaly gradually increased accompanied by increasing serum ferritin level to 10,000 ng/ml. Liver-spleen biopsy was carried out under laparoscopy and revealed infiltration of atypical histiocytes with erythrophagocytosis, which were positive for S-100 and ferritin but negative for lysozyme. The rate of glycosylation in whole serum ferritin, analyzed by using concanavalin-A binding method, showed that her glycosylated ferritin content was only 8.3%, whereas in sera after iron overloading, it was about 70%. Serum isoferritin profiles by isoelectric focussing were studied, and isoferritin pattern from malignant histiocytosis was the same as that in iron overloading after neuraminidase treatment. These findings suggest that serum ferritin is synthesized in proliferating histiocytes and released in the plasma as a nonsecretory type (nonglycosylated ferritin) in this case.

A review of 134 cervical conizations performed in a 36-month period showed that 18 were performed on patients with two or more cervical smears showing dysplasia but with essentially negative, satisfactory colposcopic evaluations, including normal colposcopically directed biopsies and endocervical curettings. A histologic diagnosis of cervical intraepithelial neoplasia (CIN) of various grades was established in 15 (83%) of the 18 conization specimens. Six (33%) of the 18 specimens harbored CIN 3. The histologic diagnosis of a more severe lesion than that indicated on cytology was rendered in five of the cases. Cervical conization should be performed when colposcopic evaluation of the cervix, vagina and vulva fails to identify the source of persistent CIN on Papanicolaou smears.

Nonuniformity of heavy-ion-beam (HIB) illumination is one of key issues in the HIB inertial confinement fusion (ICF): implosion symmetry should be less than a few percent in order to compress a fuel sufficiently and release fusion energy effectively. In this paper a new HIB illumination scheme is presented in order to realize a robust illumination scheme against a displacement of a direct-driven fuel pellet in an ICF reactor. It is known that the HIB illumination nonuniformity is sensitive to a little pellet displacement from a reactor chamber center; a pellet displacement of only 50–100μm was tolerable in the conventional HIB illumination schemes. In this paper by three-dimensional computer simulations a new robust HIB illumination scheme was found, in which a 200–300μm displacement is allowed.

A mathematical model has been developed to represent the heat transfer, the flow of the solid and molten phases and the pressure distribution in the solid phase for the twin roll rapid quenching of pure metallic materials. The following main conclusions may be drawn from these calculations, which were carried out using the property values of aluminum. If roll spacing, feed rate and angular velocity of the rolls are considered to be main variables, then for a given material there exists only a narrow range of these parameters that affords stable operation.

A mathematical model has been developed to represent the spreading of the slug and its subsequent solidification for the piston and anvil splat cooling technique. In the statement of the problem allowance has been made for fluid flow effects regarding the spreading, convective heat flow and the actual movement of the piston after the impact. In representing heat flow allowance has been made for convection for the two dimensional transient temperature fields and the existence of a mushy zone on solidification. The computed results gave predictions regarding the effect of the piston velocity and of the substrate-splat heat transfer coefficient on both the final splat thickness and on the cooling rates. It was found that the higher the piston velocity and the higher the splat-substrate heat transfer coefficient, the faster are the attainable cooling rates, although there is a tendency to approach limiting values. A critical comparison of the present work with previous modeling efforts shows marked spatial variations in the cooling rates so that the previously used one dimensional models are not likely to be satisfactory. Furthermore, the analysis of the fluid flow phenomena given in the present paper allows a realistic assessment of the final splat thickness, which was not available up to the present.

Weak two-beam common diffraction imaging (weak-beam α-fringe electron microscopy) is shown to be useful in measuring the lattice translation at an ordered interface and determining the Burgers vector of an isolated interface dislocation in thin foil specimens of stainless steel SUS 316. As an example to demonstrate the precision of the technique, a small lattice translation normal to a stacking fault introduced by hydrogen electrolysis was measured by the densitometry of the fringe shift.

The localization of creatine kinase (CK) M in canine myocardium was immunocytochemically studied by a direct immunoperoxidase method. Specific antiserum against CK-M was produced in rabbits immunized with canine CK-MM. An anti-CK-M Fab'-horseradish peroxidase conjugate was prepared by the maleimide method. Frozen sections prepared from fixed canine myocardium were stained with the conjugate and observed by light and electron microscopy. In light microscopy of longitudinal sections, CK-M showed a cross-striated pattern consisting of distinct broad and narrow brown bands. Immunoelectron microscopy revealed that the regions of the broad and narrow brown bands corresponded to the A-band and the Z-line, respectively. Most CK-M in the A-band was associated with the thick fibers, and a small amount of CK-M was found in the M-line. These findings suggest that ATP regeneration from the ADP produced by myosin ATPase is related to the participation of this CK associated with the thick fibers rather than that of the M-line-bound CK. Creatine kinase M was also found in the sarcolemmal membrane, the membranes of the sarcoplasmic reticulum, and the mitochondrial outer and inner membranes. This report provides new information for understanding the physiological role of the phosphorylcreatine shuttle in the myocardial energy transport system.

Intersubject variability in the relation between cardiac output (Q) and O2 uptake (VO2) was examined during supine cycling up to the maximum level in 40 normal untrained men age 27 +/- 4 (SD) yr. In individual subjects, Q increased linearly against VO2 in the submaximum exercise range. The SD of Q on VO2 was so small (0.47 +/- 0.25 l/min) that Q could be given by a linear function of VO2 as Q = K(VO2 - VO2 r) + Qr, where K, VO2 r, and Qr are the slope of the regression line, the resting VO2, and resting Q, respectively. K varied widely among the subjects studied, ranging from 5.5 to 10.3 and was independent of both physical characteristics and Qr, which ranged from 3.7 to 8.3 l/min. However, K correlated significantly with changes in heart rate, stroke volume, mean arterial pressure, and systemic vascular conductance. From these results, we concluded that the intersubject variability in the Q-VO2 relation was caused independently by individual variations in resting hemodynamics and in cardiovascular response to exercise.

Summary Objective We tested the hypothesis that human glucocorticoid-induced tumor necrosis factor receptor (hGITR/TR11) expressed on the surface of activated CD4 + T cells is responsible for up-regulating the production of matrix metalloproteinase (MMP)-13 by fibroblast-like synoviocytes (FLSs). Methods The level of MMP-13 was measured by Western blot and reverse transcriptase polymerase chain reaction (RT-PCR). Expressions of hGITR ligand (hGITRL) on the surface of FLSs and hGITR on the surface of human CD4 + T cells were analyzed by flow cytometry and RT-PCR. Neutralizing antibodies (Abs) were used to block hGITRL and hGITR on the surface of FLSs and human CD4 + T cells, respectively. Human CD4 + T cells were cocultured with FLSs to facilitate interaction between hGITR on CD4 + T cells and hGITRL on FLSs. Results Soluble hGITR (shGITR) stimulated FLSs to produce MMP-13, and blockade of hGITRL reduced this effect. Direct contact between activated CD4 + T and FLSs also induced the production of MMP-13, and neutralization of hGITR on activated CD4 + T cells during coculture decreased the amount of MMP-13 produced by FLSs. Conclusion shGITR stimulated FLSs to produce MMP-13 via a signal through hGITRL. Direct contact between activated CD4 + T cells and FLSs facilitated hGITR–hGITRL interaction, and resulted in inducing MMP-13. This effect may increase tissue destruction in chronic inflammation such as rheumatoid arthritis (RA).

IMPATT diodes are promising tunable sources of long submillimetre waves with reasonable output power. This paper reports a method of phase-locking IMPATT sources to a low frequency reference of high stability and low noise.