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Abstract:Objective: The present study was designed to examine the involvement of bradykinin in thermal and mechanical hyperalgesia induced by chronic constriction nerve injury (CCI) using B₁ and B₂ receptor antagonists and mutant kininogen-deficient rats. Methods: Sprague-Dawley (SD) rats and Brown Norway (B/N-) rats given CCI treatment on day 0, were used as a model of neuropathic pain. Either a kinin B₁ antagonist des-Arg⁹-[Leu⁸]-bradykinin or the receptor B₂ antagonist HOE-140 was constantly infused into the left jugular vein of SD rats on days 15 to 22 after CCI. Vehicle-treated rats and sham-operated rats without nerve injury were also prepared as controls. In all rats, we observed pain behavior, and measured the latency period of paw withdrawal from the thermal stimuli and, with von Frey filaments, the mechanical pain threshold, before surgery and on days 14 and 22 after CCI. B/N-Katholiek rats, which congenitally lack plasma kininogen and release no kinin, were also tested for hyperalgesic parameters. Expression of kinin receptor mRNA in the dorsal root ganglia was detected by RT-PCR. Results: Most of the rats (88%)showed some pain behavior, which was reduced to 67% by a B₁ antagonist and to 57% by a B₂ antagonist infused between days 15 to 22. Thermal hyperalgesia was significantly reduced from 7.25 ± 0.41 sec (mean ± SEM) to 8.36 ± 0.41 sec in paw withdrawal latency on day 22 by a B₁ antagonist and from 7.24 ± 0.19 sec to 8.23 ± 0.21 sec by a B₂ antagonist (P < 0.05). Mechanical hyperalgesia was also ameliorated from 0.02 ± 0.007 g force to 0.16 ± 0.08 g force in pain threshold by a B₁ antagonist and from 0.03 ± 0.007 g force to 0.10 ± 0.003 g force on day 22 by a B₂ antagonist. Moreover, deficient B/N-Katholiek rats showed a low incidence of thermal and mechanical hyperalgesia on day 14. Expression of both B₁ and B₂ receptor mRNAs was detected in the lumbar dorsal ganglia ipsilateral to the site of the ner ve injury. Conclusion: These data suggests that kinin were at least partly involved in yielding nociceptor hypersensitivity up to day 14 after CCI. Bradykinin and its B₁ and B₂ receptors were involved in the maintenance of hyperalgesia.

Abstract.: Pseudomonas aeruginosa resistance (minimum inhibitory concentration [MIC], ≥16 μg/ml defined as resistant) to meropenem, imipenem, panipenem, piperacillin, ceftazidime, cefozopran, cefoperazone, sulbactam/cefoperazone, amikacin, and tobramycin, as well as cross-resistance profiles, were investigated in P. aeruginosa strains isolated at eight hospitals in the Johoku area, Tokyo, during November 1998. Overall, 8.3% of isolates were imipenem-resistant and 4.6% were ceftazidime-resistant. However, the incidence of antibiotic-resistant P. aeruginosa was distinctly different at each hospital. P. aeruginosa resistance to imipenem ranged from (MIC) 1 to 64 μg/ml (MIC90 32 μg/ml), and its resistance to ceftazidime ranged from 2 to more than 128 μg/ml (MIC90, 64 μg/ml). Meropenem (MIC range, ≤0.25 to 16 μg/ml) was more active than panipenem (MIC range, 2 to 64 μg/ml). Cefozopran was more active than piperacillin, cefoperazone, or sulbactam/cefoperazone, but many strains were resistant to cefoperazone (17/57). Our analysis found cross-resistance to many beta-lactams, but the degree of cross-resistance was very variable.

Abstract: Background. The choice of treatment modalities for the post-surgical recurrence of lung cancer is still controversial despite the frequency of its occurrence. Because there are various recurrence and progression patterns in recurrent lung cancer, it is important to clarify those factors which have prognostic significance. These prognostic factors would be helpful for clinicians' decision-making in terms of treatment directions. Methods. To explore treatment directions for the post-surgical recurrence of lung cancer, we analyzed findings in 123 patients who died of recurrence, and identified factors of prognostic importance by univariate and multivariate analyses. Results. The median survival time (MST) and 1-year, 2-year, and 3-year survival rates of the 123 patients were 218 days and 30.8%, 13.8% and 3.3%, respectively. The survival time according to the first relapse site was examined, and lung was most favorable (MST, 353 days). Liver and bone were unfavorable (MST, 188 and 166 days, respectively). On univariate analysis, patients with a relapse-free period of 1 year or more after surgery survived for significantly longer than patients who developed recurrence less than 1 year after surgery (MST, 286 days vs 190 days, respectively; P < 0.01). On multivariate analysis, the relapse-free period proved to be the most important prognostic factor. Conclusion. We suggest that patients who develop recurrence 1 year or more after surgery may be better off being followed-up with supportive measures, rather than with chemotherapy, because they have a relatively favorable prognosis.

Abstract: Background. Docetaxel is one of the most active agents used in the treatment of advanced non-small-cell lung cancer. This phase I study was performed to determine the toxicities, maximum tolerated dose, and pharmacokinetics of the combination of docetaxel and cisplatin in patients with non-small-cell lung cancer, and to recommend a dose for phase II study. Methods. Patients were required to have previously untreated metastatic non-small-cell lung cancer, an Eastern Cooperative Oncology Group performance status of 2 or less, be aged between 15 and 74 years, to have a measurable lesion, and to have adequate organ function. Treatment consisted of 1-h infusion of docetaxel on day 1, followed by 2-h infusion of cisplatin (3 h after docetaxel) at the following docetaxel/cisplatin (mg/m2) dose levels: 50/50, 60/50, 60/60, 60/70, and 60/80. At least three patients were accrued at each dose level. Treatment was repeated every 3 to 4 weeks for responders. Administration of granulocyte-colony stimulating factor was permitted when leukocytopenia or neutropenia of grade 3 or more occurred. Results. Of the 29 patients entered, all were assessable for toxicity and response, but 2 were excluded from analyses of dose-limiting toxicity and maximum tolerated dose. Neutropenia (grade 4, for 3 days or more; n = 1), hepatic dysfunction (grade 3 or more; n = 2) and renal dysfunction (grade 2 or more; n = 3) were observed as dose-limiting toxicities. However, the maximum tolerated dose was not detected, even at the highest dose examined. Tumor response occurred in 13 of the 29 patients (45%; 95% confidence interval; 26%–64%). The pharmacokinetic profiles of docetaxel and cisplatin (n = 17) were similar to those observed after the administration of each dose as a single agent. Conclusion. Docetaxel/cisplatin doses of 60/80 mg/m2 were recommended for phase II study, because grade 4 neutropenia occurred in 50% or more patients at docetaxel/cisplatin dose levels of 60/60 mg/m2 and above, and the doses of these drugs were restricted to within the approved dose ranges for single-agent use in Japan. The responses observed in this phase I study suggest a high degree of activity of this combination against previously untreated advanced non-small-cell lung cancer and warrant a phase II study at the recommended dose level.

We investigated the profound involvement of chymase, an alternative angiotensin II-generating enzyme, in angiogenesis using a hamster sponge implant model. In vivo transfection of human pro-chymase cDNA or a direct injection of purified chymase into the sponges implanted resulted in marked increment of hemoglobin contents in the sponge granuloma tissues, demonstrating that chymase has an ability to elicit angiogenesis and is a potent angiogenic factor. Daily injection of basic fibroblast growth factor into the sponges implanted also induced angiogenesis, which was suppressed by the treatment with chymostatin, an inhibitor of chymase, or TCV-116, an antagonist of angiotensin II (Ang II) type 1 receptor. Expression of chymase mRNA and production of Ang II in the granuloma tissues were enhanced by the stimulation with basic fibroblast growth factor. Chymase activity in the sponge granulomas increased in parallel with the rise in hemoglobin contents, and mast cells observed in the granuloma tissues were positively stained with anti-chymase antibody. Exogenous administration not only of Ang II but of angiotensin I (Ang I) directly into the sponges could enhance angiogenesis. Chymostatin inhibited the angiogenesis induced by Ang I but not Ang II, suggesting the presence of a chymase-like Ang II-generating activity in the sponge granulomas. Our results may suggest a potential ability of chymase to promote angiogenesis through the local chymase-dependent and angiotensin-converting enzyme-dependent Ang II generating system in pathophysiological angiogenesis.

Abstract: A gastric stromal tumor was found in a 61-year-old man. The patient was treated by total gastrectomy, but the tumor recurred, 26 months after surgery, in the peritoneal cavity at the anastomotic site of the esophagojejunostomy, with metastases to mesenteric lymph nodes. This second tumor was removed surgically, but, 7 years after the gastrectomy, multiple recurrent tumors were found in the peritoneal cavity; once again the tumors were removed. Although the recurrent tumors were surgically removed twice, the patient died of the disease 8 years after the initial surgery. Histologically, the gastric tumor consisted of spindle-shaped neoplastic cells arranged in interlacing tumor bundles with frequent mitotic figures (four mitoses per ten high-power fields). Although the recurrent tumors also consisted of spindle-shaped neoplastic cells, myxoid changes were prominent. Immunohistochemically, the neoplastic cells gave diffuse positive reactions only with antibodies CD34 and vimentin among a variety of antibodies tested. Ultrastructural analysis failed to provide conclusive evidence for the neural or muscular origin of the tumor. The gastric tumor was therefore considered to be gastric stromal tumor of uncommitted type with malignant behavior. The patient survived for a long-term period after the gastrectomy, followed repeated removal of the recurrent tumors.

Pyrococcus furiosus has an operon containing the DNA polymerase II (PolD) gene and three other genes. Using a two-hybrid screening to examine the interactions of the proteins encoded by the operon, we identified a specific interaction between the second subunit of PolD (DP1) and a Rad51/Dmc1 homologous protein (RadB). To ensure the specific interaction between these two proteins, each gene in the operon was expressed in Escherichia coli or insect cells separately and the products were purified. The in vitro analyses using the purified proteins also showed the interaction between DP1 and RadB. The deletion mutant analysis of DP1 revealed that a region important for binding with RadB is located in the central part of the sequence (amino acid residues 206-498). This region has an overlap to the C-terminal half (amino acids 334-613), which is highly conserved among euryarchaeal DP1s and is essential for the activity of PolD. Our results suggest that, although RadB does not noticeably affect the primer extension ability of PolD in vitro, PolD may utilize the RadB protein in DNA synthesis under certain conditions.

beta1-null GD25 fibroblasts adherent to vitronectin fail to bind the N-terminal 70-kDa matrix assembly domain of fibronectin or to assemble fibronectin (Sakai, T., Zhang, Q., Fässler, R., and Mosher, D. F. (1998) J. Cell Biol. 141, 527-538). We have made four observations that extend this finding. First, the presence of vitronectin on a substrate that otherwise can support fibronectin assembly has a dominant-negative effect on assembly. Second, the dominant-negative effect is lost when active beta1A is expressed. Third, beta1A containing the extracellular D130A inactivating mutation has a dominant-negative effect on fibronectin assembly. Fourth, beta1-null cells adherent to vitronectin are flat and lack filopodia, whereas beta1-null cells adherent to fibronectin or beta1A-expressing cells adherent to either vitronectin or fibronectin are contracted and exhibit numerous filopodia. These results reveal, therefore, that GD25 cells adherent to vitronectin can only assume a shape suitable for assembly of fibronectin when there is a countervailing signal from functional beta1-integrins.

Measurements of take-off velocities under various conditions were carried out in order to explain the fact that a 70 percent microslider gave better performance on CSS than a 100 percent mini slider. It was found that take-off speeds increased as the radii of CSS tracks decreased. On a 65 mm disk, use of a mini slider could result in 40 percent higher take-off velocity when the CSS track was moved from a 25 mm radius to 18 mm radius. The main contributor to this increase was found to be clamping effect. Clamping force changed the local curvature of a disk within the 2 mm range, and it overshadowed surface roughness of a disk. It was also demonstrated that stable sliders, such as a microslider or a slider with a high had, were less vulnerable to clamping effect. CSS tests confirmed that higher clamping force could drastically deteriorate CSS durability.

Adipose conversion of cultured 3T3 cells is known to depend on an adipogenic factor present in serum. In the presence of this factor, extracts of different organs were found to inhibit the adipose conversion. The most active extracts were derived from brain, uterus, and pituitary, but other organs also possessed appreciable activity. Fibroblast growth factor partially purified from both brain and pituitary was much more active in suppressing adipose conversion than were crude extracts of the corresponding organs. Purified platelet-derived growth factor was also an effective inhibitor. Of all the tissue extracts tested, only pituitary possessed, in addition to the inhibitory activity, an adipogenic factor similar to that demonstrated previously in serum. This was revealed at concentrations of extract too low for the inhibitory factor to be effective. Under these conditions the pituitary extract had a specific adipogenic activity orders of magnitude higher than that of serum. We suggest that the adipogenic factor of serum may originate in the pituitary.

Choosing a thick circular plate with a solid shaft as a simple model of gear blanks, the authors have developed a theoretical method for accurately estimating the noise power radiated from gear blanks during the design phase. To model analytically the natural modes of damped flexural vibration of the circular plate, a diagonal matrix equation was derived from Mindlin's equations for thick plates. Also, approximate spring constants required for an elastic boundary condition were derived in order to calculate the natural modes of flexural vibration as precisely as possible. Almost correct natural modes have been obtained: the natural frequencies and mode shapes calculated with the elastic boundary condition compare well with those obtained from experimental modal analysis and analytical modal analysis by a finite element method. Copyright 1994, 1999 Academic Press

Lung Cancer Associated Protein (LCAP) is a high molecular weight glycoprotein defined by the monoclonal antibody (MAb) DF-L1 prepared against a primary adenocarcinoma of the lung. Previous studies have demonstrated that LCAP circulates at elevated levels in patients with lung cancer. However, a suitable assay for monitoring LCAP levels has not been available. The present work describes the development of a double-determinant LCAP assay using MAb TRD-L1 as the capture antibody and MAb DF-L1 as the tracer. In 60 normal subjects, the mean LCAP level was 4.8 U/ml with 2 (3.3%) subjects having values >12 U/ml (mean + 2SDS). By contrast, 37 of 67 (55.2%) patients with lung cancer had LCAP levels >12 U/ml. Moreover, only 14 of 203 (6.9%) patients with benign lung disease had elevated levels. LCAP levels were most commonly elevated (62.7%) in patients with adenocarcinoma of the lung and with advanced disease. These results indicate that LCAP as detected by MAb TRD-L1 is a potentially useful marker for the evaluation of patients with lung cancer.

To be able to deseribe the structure and functioning of Miscanthus sinensis grassland, its floristie composition, life-form spectra, stand productivity and dry matter allocation were studied. 43 species were to be found during the growing season of 1976. 29 species, and 345 individuals per 1 m2, were observed in the sample areas in September. The values for standing crop of constituent species have been arranged in ascending order. The dominant Raunkiaer life-forms were the hemicryptophyte and geophyte. The stand was characterized by erect and tufted forms in Numata's system of growth form classification. The standing crop of the whole stand decreased from April to June, then increased from mid-July. The maximum standing crop of 3346 g m-2was observed in September. The net production of the stand was 959.4 g m-2year-1. Fifty one percent of this net production was allocated to the underground organs which consume it for respiration during winter and for initial growth in the next growing season.

High-molecular-weight kininogen has been isolated from rat plasma in three steps in a relatively high yield. The purified preparation gave a single band on sodium dodecyl sulfate-polyacrylamide gel electrophoresis in the absence and presence of 2-mercaptoethanol, and the apparent Mr was estimated as 100,000. On incubation with rat plasma kallikrein, rat high Mr kininogen yielded a kinin-free protein consisting of a heavy chain (Mr = 64,000) and a light chain (Mr = 46,000), liberating bradykinin. The kinin-free protein was S-alkylated, and its heavy and light chains were separated by a zinc-chelating Sepharose 6B column. The amino acid compositions of rat high Mr kininogen and its heavy and light chains were very similar to those of bovine high Mr kininogen and its heavy and fragment 1.2-light chains, respectively. A high histidine content in the light chain of rat high Mr kininogen indicated the presence of a histidine-rich region in this protein as in bovine high Mr kininogen, although this region was not cleaved by rat plasma kallikrein. Rat high Mr kininogen corrected to normal values the prolonged activated partial thromboplastin time of Brown-Norway Katholiek rat plasma known to be deficient in high Mr kininogen and of Fitzgerald trait plasma. The kinin-free protein had the same correcting activity as intact high Mr kininogen. Rat high Mr kininogen also accelerated approximately 10-fold the surface-dependent activation of rat factor XII and prekallikrein, which was mediated with kaolin, amylose sulfate, and sulfatide. These results indicate that rat high Mr kininogen is quite similar to human and bovine high Mr kininogens in terms of biochemical and functional properties.

We report a remarkable Fe K? fluorescence line profile in the Seyfert 1.9 galaxy MCG -5-23-16. The line is complex, consisting of a narrow core located at the galaxy's systemic velocity and wings to the red and blue sides of the core. This represents only the second detection with ASCAof an Fe K? line profile with significant broadening blueward of 6.4 keV, consistent with Doppler boosting. The line core has an EW of ~60 eV and the wings have a combined EW of ~200 eV. The entire profile cannot be easily modeled with an emission line predicted from standard accretion disk theories. Instead, the line is marginally triple-peaked and is best described with three Gaussians having rest energies of 5.37+ 0.23?0.19keV (FWHM = 30,200 km s-1), 6.37 ± 0.04 keV (FWHM < 6,600 km s-1), and 6.58+ 0.35?0.38keV (FWHM = 75,300 km s-1). The line can also be modeled with a narrow Gaussian at ~6.4 keV and an emission line from an accretion disk viewed at an inclination angle of ~30° to 65°, depending on the ionization state of the gas. Within the context of the unified model, the most likely physical description of the complex profile is a superposition of an emission line from an accretion disk and a line that arises far from the disk in either the obscuring torus or the broad line region. This represents the first strong evidence for emission from two distinct X-ray reprocessors within a single Seyfert 1-type galaxy.

Antibacterial activities of cefotaxime and its major metabolite, desacetylcefotaxime, against 178 strains (of 10 species) were assessed in terms of minimum inhibitory concentrations (MIC50and MIC80), and were compared with those of cefoperazone and ceftazidime. The activity of desacetylcefotaxime was several times less than that of cefotaxime against almost all of the species tested. Against Staphylococcus aureus, Morganella morganii, Enterobacter cloacaeand Pseudomonas aeruginosa, the M1C8O values of desacetylcefotaxime were higher than those of cefoperazone and ceftazidime. The antibacterial potency of desacetylcefotaxime against Klebsiella pneumoniaeand Pseudomonas cepaciawas superior to that of cefoperazone and ceftazidime, and comparable with the activities of the latter compounds against the other 4 Gramnegative species. Partial synergy was demonstrated in the activity of cefotaxime and desacetylcefotaxime against most of the strains examined. Antagonism was observed in activity against 2 of 18 strains of M. morganii. In general, desacetylcefotaxime enhances the potency of its parent compound, cefotaxime, when they coexist. Intravenous infusion of cefotaxime Ig over a period of 1 hour resulted in mean peak serum concentrations of 48.5 mg/L of cefotaxime and 6.5 mg/L of desacetylcefotaxime at the end of the infusion. The mean elimination half life in β-phase of cefotaxime was 0.8 hour and that of desacetylcefotaxime was 2 hours.

Seventeen patients with craniofacial synostosis (CFS) have been treated at the Department of Plastic and Reconstructive Surgery at Osaka Medical College during the past 10 years. Six patients were thoroughly evaluated at the Department of Otolaryngology by polysomnography (PSG), cephalometric X-ray and nasopharyngoscopy during sleep. In 4 of the patients PSG showed obstructive sleep apnea syndromes (OSAS). Heavy snoring without apnea and paradoxical respiration were noted in the other 2 patients. Thus, all of the patients had sleep-related breathing disorders (SRBD). It is assumed that the incidence of SRBD in CFS is high. Cephalometric analysis and profilogram showed maxillomandibular hypoplasia in each patient, and it was assumed that the main cause of SRBD in CFS was stenosis of the upper airway tract caused by maxillo-mandibular hypoplasia. Nasopharyngoscopy was performed during sleep in 2 patients with OSAS secondary to CFS. One patient with adenotonsillar hypertrophy had nasopharyngeal obstruction and another patient whose posterior airway space (PAS) on cephalometric radiograph was 3 mm (normal value: 11 mm) had obstruction at the tongue base.

The aim is to establish a method for accurately estimating gear noises radiated by the flexural vibration of gear blanks. The basic theory from which is derived the frequency characteristics of radiated sound power is presented. First, the basic theory for estimating radiated and sound power is derived from the definition of loss factor given by Ungar and Kerwin and is confirmed to apply at all frequencies. Second, a thick circular plate with a solid shaft is chosen as a simple model of gear blanks. The natural modes of flexural vibration of the circular plate have been theoretically analyzed in the companion paper [1]; the rigid body modes of vibration of the circular plate are theoretically analyzed in this paper. These analyses produce formulae for deriving the frequency characteristics of three important factors for estimation: the total loss factor, driving point mobility and radiation loss factor of the circular plate. To examine the estimation formula and the associated formulae, experimental data is obtained by impulsively exciting the circular plate in the axial direction, and then measuring the intensity of the radiated sound power. The three important factors for estimating this power (the total loss factor, the driving point mobility and the radiation loss factor of the circular plate) are calculated from the theoretical formulae, and the sound power is then estimated by substituting the measured excitation force into the estimation formula. The estimated radiated sound power agrees well with the measured values both in the low and high frequency ranges where the rigid body modes and the natural modes of flexural vibration exist, respectively. Copyright 1994, 1999 Academic Press

Two T-kininogens (TI- and TII-kininogens) found in plasma of Freund's adjuvant-treated rats were purified by several chromatographic procedures. The isolated TI- and TII-kininogens showed different mobilities on polyacrylamide gel electrophoresis in the absence of sodium dodecyl sulfate, but were indistinguishable in the presence of sodium dodecyl sulfate. They were also indistinguishable in amino acid composition and antigenicity, but differed in sialic acid content. The NH2- and COOH-terminal sequences were determined. In the 30 NH2-terminal residues, 2 were different. The kinin regions in the COOH-terminal portions of the two kininogens have sequences that demonstrate TI-kininogen contains a mixture of two kinin-containing regions, with substitution of 4 amino acid residues, one of which is identical to the COOH-terminal portion of alpha 1-major acute phase protein (Cole, T., Inglis, A. S., Roxburgh, C. M., Howlett, G. J., and Schreiber, G. (1985) FEBS Lett. 182, 57-61) and the other to the COOH-terminal portion of TI-kininogen (Furuto-Kato, S., Matsumoto, A., Kitamura, N., and Nakanishi, S. (1985) J. Biol. Chem. 260, 12054-12059), both predicted from cDNA sequences. The amino acid sequence of the kinin-containing region from TII-kininogen is the same as the COOH-terminal portion of TII-kininogen predicted from the cDNA. These results indicate that T-kininogens from the plasma of adjuvant-treated rats consist of a family of kininogens, that is, TI- and TII-kininogens (separable on DEAE-Sephadex A-50), and that TI-kininogen consists of at least two variants (TI alpha and TI beta) which correspond to the alpha 1-major acute phase protein reported by Cole et al. and TI-kininogen reported by Furuto-Kato et al., respectively. Immunoblotting studies with plasmas from non-inflamed and adjuvant-treated rats also indicate that T-kininogen which was previously isolated from non-inflamed rat plasma corresponds to TI-kininogen and that TII-kininogen is newly generated after treatment of rats with adjuvants.

Two kinds of low molecular weight kininogens (identified as A and B) were isolated from pooled plasma of Sprague-Dawley rats. They show a single band on sodium dodecyl sulfate-polyacrylamide gel electrophoresis in the presence and absence of 2-mercaptoethanol, and the molecular weights are 68,000 for low Mr kininogen A and 73,000 for low Mr kininogen B. Although the molecular weights and amino acid compositions of the low Mr kininogens are similar, rat submaxillary and urinary kallikreins released bradykinin from low Mr kininogen B, whereas low Mr kininogen A was resistant to these enzymes. The COOH-terminal portion of low Mr kininogen A was isolated after cyanogen bromide treatment, and the amino acid sequence of the COOH-terminal 55 residues including the T-kinin (Ile-Ser-bradykinin) was determined. The COOH-terminal portion consists of two sequences with substitution of 4 residues. One peptide corresponds to alpha 1-major acute phase protein (Cole, T., Inglis, A. S., Roxburgh, C. M., Howlett, G. J., and Schreiber, G. (1985) FEBS Lett. 182, 57-61) and the other to the TI-kininogen predicted from a cDNA study (Furuto-Kato, S., Matsumoto, A., Kitamura, N., and Nakanishi, S. (1985) J. Biol. Chem. 260, 12054-12059). The results demonstrate that there exist at least two kinds of low Mr kininogens with clearly different function in rat plasma: one of them, low Mr kininogen A, is a precursor of T-kinin and is resistant to kallikreins, and the second, low Mr kininogen B, is sensitive to tissue kallikreins and shares properties with bovine and human low Mr kininogens. The results also demonstrate that T-kininogen is a mixture of two isoproteins which correspond to alpha 1-major acute phase protein or TI-kininogen, respectively. We could not detect the low Mr kininogen corresponding to the TII-kininogen predicted from the cDNA study of Furuto-Kato et al.

As an approach to the treatment of patients with large but circumscribed akinetic or dyskinetic regions in the left ventricular myocardium as sequelae of acute myocardial infarction, excision of the defect and implantation of a mechanical functional equivalent of myocardium is suggested. Experimental investigation of this technique is described.Hemodynamic data from a series of dog experiments indicate that activation of the prosthetic myocardium after excision of the left ventricle is followed by improvement in various hemodynamic parametres of interest Although substantial experimental work must be completed and difficult bioengineering problems solved, preliminary results have encouraged us to continue our investigations of the prosthetic myocardium.An imposing array of treatment methods is now available to the clinician who must deal with the sequelae of acute myocardial infarction. Selecting from pharmacologic, electrophysiologic, and surgical approaches the physician can in many instances design a treatment plan precisely tailored to the clinical problem.Large left ventricular aneurysms and their functional equivalents of ventricular dyskinesis or hypokinesis continue, however, to represent a class of problems in which established techniques have been less then satisfactory. Surgical excision with closure of the defect is regarded as effective for small aneurysms, but such procedures may so compromise cardiac output in patients with large ones as to be unacceptable. Unfortunately, it is just the latter group in which medical palliation is least likely to be effective in managing congestive failure, angina, and other pathophysiologic manifestations.A relatively unsual approach derived from in-series techniques of mechanical assistance to the failing circulation (1) offers the theoretical possibility of a treatment tailored to the problem of a large ventricular aneurysm. Experimental investigation of this technique in the Surgical Research Laboratory at the Sinai Hospital of Detroit has progressed to the point that a report of our experiences to date may be of interest.

A role of renal angiotensin-converting enzyme (ACE) in diabetic nephropathy has been suggested. Immunohistochemical localization of ACE was studied in 20 non-insulin-dependent diabetes mellitus patients with diabetic nephropathy and 17 healthy kidney transplant donors, with ACE gene insertion/deletion (I/D) polymorphism also examined in the latter. Immunohistochemical studies indicated that ACE staining was significantly (P < 0.01) enhanced in glomeruli and slightly decreased in proximal tubules in diabetic patients. Glomeruli positive for ACE immunostaining were observed in 23.5% of the healthy subjects and in 80% of the diabetic patients. All patients with nodular lesions had ACE- positive glomeruli and showed significantly (P < 0.01) more intense glomerular ACE immunostaining than patients without nodular lesions. Among healthy controls, subjects with the DD genotype had ACE-positive glomeruli more frequently and tended to show slightly increased intensity on proximal tubule ACE immunostaining compared with subjects with other genotypes. These observations suggest that increased ACE localization in glomeruli is likely to be one of the factors in the increased renin-angiotensin system activity in glomeruli in patients with diabetic nephropathy. There is a possibility that ACE gene I/D polymorphism may be related to renal ACE immunohistochemical localization. (Am J Kidney Dis 1998 Feb;31(2):301-7)

Summary: Serum is the last undefined component in cell culture media. Our results indicate that the primary role of serum is to provide hormones and that serum can be replaced by a group of hormones. A rat pituitary cell line, GH3, can grow in serum-free medium if the medium is supplemented with 3,3′,5-triiodothyronine, TSH-releasing hormone, transferrin, parathyroid hormone, insulin and three isoelectric focusing fractions of blood meal. The blood-meal components can be replaced by fibroblast growth factor and somatomedin C. The growth rate of GH3 cells in hormone-supplemented serum-free medium is equal to that in serum-supplemented medium, and subculture in such medium is also possible. These results indicate that the replacement of the serum component is complete in the GH3 system. The hormonal requirements of GH3 cells and those of HeLa and mouse melanoma, M2R, were compared. Two generalizations could be made: (a) All three cell lines require insulin and transferrin. (b) There is a requirement for a hormone which localizes in the nucleus for each cell line. These generalizations seem to hold true for most of the other cell lines for which the hormonal requirements have been partially worked out. Since insulin is one of the universally required hormones, its effects on GH3, HeLa and M2R were compared. Insulin stimulates glycogen synthesis in all three cell lines and facilitates fatty-acid synthesis in GH3 and M2R. However, there is a difference in the effect of insulin on growth among the three cell lines. Insulin is an absolute requirement for GH3 cells without which the cells cannot survive, whereas this is not the case for HeLa and M2R. The most stringent requirement for HeLa cells is for hydrocortisone, and for M2R, it is for transferrin. These results indicate that even though the necessity for some hormones is common, the degree of requirement may vary from one cell line to another. Whether this difference reflects the difference in the primary mode of action of the hormone on each cell type needs further investigation.

The origin of urinary bradykinin was defined by use of plasma kininogen deficient B/N-Katholiek rats, whose ureter urine contains very low amount of urinary kinin. The kinin level increased after the rats received an infusion of normal plasma. Furthermore, the bradykinin content in the ureter urine of these kininogen-deficient rats increased more by infusion of partially purified rat low-molecular-weight kininogen than by that of high-molecular-weight kininogen. Urinary kallikrein activity of B/N-Katholiek rats was enzymatically identical with that of normal B/N-Kitasato rats. These results indicate that urinary bradykinin found in the ureter urine of normal rats is derived from plasma low-molecular-weight kininogen by cleavage by urinary kallikrein.

The molecular beam method is a versatile experimental technique which may be used to grow high quality single crystal thin films in the range from 100Å to several microns with precise control of uniformity and thickness. Films may be doped by an additional molecular beam containing the doping material simultaneously impinging on the substrate surface with the film molecular beams. Epitaxial GaAs thin films doped with silicon were grown by the molecular beam method in an ultrahigh vacuum system in which high energy electron diffraction and mass spectrometric measurements could be made during growth or by stopping growth momentarily. The crystallinity and beam intensity parameters of these films were thus studied during growth. The doping profiles and the amount of compensation were evaluated by the Schottky barrier diode method and the photo luminescence spectra.

The concept that multilayer structures containing several heterojunctions may be used as low threshold lasers has led to the development of techniques for the preparation of such structures by liquid phase epitaxy. This development of LPE techniques for the successive growth of thin (< 1 to ≈4ώm) layers of GaAs and AlxGa1−xAs, and thus the preparation of lasers which with adequate heat sinking operate continuously at room temperature, is described in detail.

Carrageenin-induced paw edema in HMW- and LMW-kininogens-deficient rats was significantly less than that in normal rats. There are three kiniogens, HMW-, LMW- and T-kininogens, in normal rat plasma, but B/N-Katholiek rat plasma contains only T-kininogen. The pretreatment with captopril, a kiniase II inhibitor, enhanced paw swelling of normal rats, but not that of the deficient rats, indicating that bradykinin released from HMW-kininogen may have a role for the swelling but T-kinin may not be released in this inflammation.