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Head-to-body stunning is regarded as 'best practice' stunning for sheep. The benefits are loss of consciousness followed by cardiac arrest, death, prevention of animal movements post stunlkill and improved meat quality. Commercial equipment places electrodes on the head and back, which is known to cause pelt burning, thus reducing the value of the skins. The aim was to demonstrate that passing current at 1.5 A and 50 Hz from the top of the head to the chest in lambs for 3.1 s would result in epilepsy. Electroencephalographic (EEG) and electrocardiographic (ECG) activity was recorded in sheep using non-invasive electrodes. Measurements in this trial were successfully performed on three lambs (live weight 25 to 39 kg) which were anaesthetised and given neuromuscular blockers to inhibit muscle activity. EEG information showed that the head-to-chest stunning produced an epileptic-like episode, which was followed by an isoelectric output. ECG recordings showed that ventricular fibrillation (VF) was induced and coincided with the epileptic brain activity observed. No animals regained brain activity or sinus heart rhythm after applying the stated stunning conditions. As a conclusion, it is postulated that modified stunning equipment passing an electrical current from the top of the head to the sternum in lambs (1.5 A, 50 Hz; 3.1 s) may induce an epileptic seizure and VF. [ABSTRACT FROM AUTHOR]

The Banff Working Group on Liver Allograft Pathology reviewed and discussed literature evidence regarding antibody-mediated liver allograft rejection at the 11th (Paris, France, June 5–10, 2011), 12th (Comandatuba, Brazil, August 19–23, 2013), and 13th (Vancouver, British Columbia, Canada, October 5–10, 2015) meetings of the Banff Conference on Allograft Pathology. Discussion continued online. The primary goal was to introduce guidelines and consensus criteria for the diagnosis of liver allograft antibody-mediated rejection and provide a comprehensive update of all Banff Schema recommendations. Included are new recommendations for complement component 4d tissue staining and interpretation, staging liver allograft fibrosis, and findings related to immunosuppression minimization. In an effort to create a single reference document, previous unchanged criteria are also included.

ZFP521was previously identified as a putative gene involved in induction of B-cell lymphomagenesis. However, the contribution of ZFP521to lymphomagenesis has not been confirmed. In this study, we sought to elucidate the role of ZFP521in B-cell lymphomagenesis. To this end, we used a retroviral insertion method to show that ZFP521was a target of mutagenesis in pre-B-lymphoblastic lymphoma cells. The pre-B-cell receptor (pre-BCR) signaling molecules BLNK, BTKand BANK1were positively regulated by the ZFP521gene, leading to enhancement of the pre-BCR signaling pathway. In addition, c-mycand c-junwere upregulated following activation of ZFP521. Stimulation of pre-BCR signaling using anti-Vpreb antibodies caused aberrant upregulation of c-mycand c-junand of Ccnd3, which encodes cyclin D3, thereby inducing the growth of pre-B cells. Stimulation with Vpreb affected the growth of pre-B cells, and addition of interleukin (IL)-7 receptor exerted competitive effects on pre-B-cell growth. Knockdown of BTKand BANK1, targets of ZFP521, suppressed the effects of Vpreb stimulation on cell growth. Furthermore, in human lymphoblastic lymphoma, analogous to pre-B-cell lymphoma in mice, the expression of ZNF521, the homolog of ZFP521in humans, was upregulated. In conclusion, our data showed that the ZFP521gene comprehensively induced pre-B-cell lymphomagenesis by modulating the pre-B-cell receptor signaling pathway.

We evaluated the effects of rituximab prophylaxis on outcomes of ABO-blood-type-incompatible living donor liver transplantation (ABO-I LDLT) in 381 adult patients in the Japanese registry of ABO-I LDLT. Patients underwent dual or triple immunosuppression with or without B cell desensitization therapies such as plasmapheresis, splenectomy, local infusion, intravenous immunoglobulin and rituximab. Era before 2005, intensive care unit-bound status, high Model for End-Stage Liver Disease score and absence of rituximab prophylaxis were significant risk factors for overall survival and antibody-mediated rejection (AMR) in the univariate analysis. After adjustment for era effects in the multivariate analysis, only absence of rituximab prophylaxis was a significant risk factor for AMR, and there were no significant risk factors for survival. Rituximab prophylaxis significantly decreased the incidence of AMR, especially hepatic necrosis (p < 0.001). In the rituximab group, other B cell desensitization therapies had no add-on effects. Multiple or large rituximab doses significantly increased the incidence of infection, and early administration had no advantage. In conclusion, outcomes in adult ABO-I LDLT have significantly improved in the latest era coincident with the introduction of rituximab.

Blockade of the CD40–CD154 costimulatory signal is an attractive strategy for immunosuppression and tolerance induction in organ transplantation. Treatment with anti‐CD154 monoclonal antibodies (mAbs) results in potent immunosuppression in nonhuman primates (NHPs). Despite plans for future clinical use, further development of these treatments was halted by complications. As an alternative approach, we have been focusing on the inhibition of the counter receptor, CD40 and have shown that a novel human anti‐CD40 mAb, ASKP1240, markedly prolongs renal allograft survival in NHPs, although allografts eventually underwent chronic allograft nephropathy. On the basis of our previous findings that a CD40–CD154 costimulation blockade induces tolerance to hepatic, but not cardiac, allografts in rodents, we tested here our hypothesis that a blockade of CD40 by ASKP1240 allows acceptance of hepatic allografts in NHPs. A 2‐week ASKP1240 induction treatment prolonged liver allograft survival in NHPs; however, the graft function deteriorated due to chronic rejection. In contrast, a 6‐month ASKP1240 maintenance monotherapy efficiently suppressed both cellular and humoral alloimmune responses and prevented rejection on the hepatic allograft. No serious side effects, including thromboembolic complications, were noted in the ASKP1240‐treated monkeys. We conclude that CD40 blockade by ASKP1240 would be a desirable immunosuppressant for clinical liver transplantation.

To overcome severe donor shortage, Japanese doctors over the years have developed innovative strategies to maximize organs transplanted per brain death donor and expanded the donor pool using living donors. They also used living and marginal organs and drastically improved living donor lung, liver, pancreas and kidney transplantations. Moreover, they initiated ABO blood type incompatible liver transplantation advancements and succeeded in overcoming the blood type barrier in kidney and liver transplantations. Similar efforts are underway for pancreas transplantation. Furthermore, Japanese doctors have developed a nonaggressive step to achieve immunosuppression following organ transplantation by carefully monitoring donor-specific hyporesponsiveness and infectious immunostatus. However, the institution of amendments to allocation systems and the intensification of efforts to decrease living donor morbidity and to increase the number of brain death donors have remained important issues needing attention. Overall, the strategies Japan has adopted to overcome donor shortage can provide useful insights on how to increase organ transplantations.

The aim of this report is to assess the rate of portal vein complications (PVCs), the success rate of treatment for PVCs and the prognosis of patients with PVCs for pediatric living donor liver transplantation (LDLT). Pre- and postoperative records of 521 pediatric LDLTs, using left-side grafts were retrospectively reviewed. The overall rate of PVC was 9, with early PVC occurring in nine patients (1.7) with a mortality rate of 67 and late PVC in 38 patients (7.3). Fifteen of these patients with late PVC showed complete portal vein occlusion despite various treatments, and in six of them the graft was lost. Histological examination revealed fibrosis in portal areas in 13 patients, around the central veins associated with cholestasis in the parenchyma in 10, and hepatocyte ballooning in 12.

Hepatitis C virus reinfection after liver transplantation is universal and more severe than in nontransplant patients. Rejection episodes and immunosuppressive agents are considered risk factors for deterioration of recurrent hepatitis C. We report 2 cases of living donor liver transplantation for patients with hepatitis C-related cirrhosis who received right-lobe grafts from an identical twin. Thanks to genetic identity, no immunosuppressive drugs were administered during or after transplantation without rejection. Hepatitis C virus RNA kinetics showed a rapid increase following transplantation and liver biopsies 1 month after transplantation showed acute lobular hepatitis in both cases. Antiviral therapy using interferon α and ribavirin was started immediately, and both cases showed virological and histological response. In conclusion, avoidance of immunosuppression did not delay hepatitis C recurrence following transplantation, while early antiviral therapy without risk of rejection or immunosuppression led to successful viral eradication.

The inhomogeneous structure of agar gels was examined by means of mechanical-scanning probe microscopy. Several domains were observed in the elasticity images, while such domains could not be seen in the height images. The domain size decreased with increases in agar concentration. We found that the histograms of the logarithm of the local elastic modulus were described well by a single normal distribution. As the agar concentration increased, the peak values of the histograms increased, while the half-value width remained constant. These results imply that the gelation process of agar gels has a common mechanism, despite its complexity.

AbstractThis article focuses on the development and evaluation of the hyper-media computer-mediated learning (CML) system for programming language. The rapid increase in the need for new software requires many programmers. As a result, programming language education has become an important theme in current education programs. Using computers in education is considered to be one of the most promising learning methods. In order to use computers in education, the following problems should be solved: (1) Exercise support:exercise plays an important role in programming language education. However, few conventional CML systems have this facility. (2) Improving teaching materials:conventional teaching materials consist of multimedia data such as text, sound, and still and motion picture. However, the paths of learning are usually fixed. The users need to follow predefined learning paths. In this article, in order to solve the second problem, the hypermedia CML system is proposed. This system, called HIMAT, adopts the following method: (a) unified processing method for the combination of multiple time-dependent data and operations; (b) extension of object-oriented programming language to deal with multimedia data; and (c) metaphor interface and ladder structure teaching material, the conceptual structure of multimedia teaching material, to improve the usability of hyper-media teaching materials. The evaluation of HIMAT and guidelines for designing hypermedia teaching materials derived from the evaluation are also described.

An 11-month-old boy with acute lymphoblastic leukemia (ALL) underwent umbilical cord blood transplantation (CBT) from an unrelated donor after a first complete remission. Despite the prophylactic use of low molecular weight heparin, prostaglandin E1 and ursodeoxycholic acid, hepatic veno-occlusive disease (VOD) occurred on the 29th day after CBT. Furthermore, neither defibrotide nor antithrombin-III improved the hepatic coma and coagulopathy due to the hepatic VOD. On the 42nd day after CBT, he underwent living related liver transplantation (LRLT) with a left lateral segment graft from his father. He received tacrolimus for the prevention of rejection and graft-vs.-host disease (GVHD) and also received aggressive antifungal and antiviral prophylaxis. Although he showed signs of acute rejection on postoperative days 5 and 10, the postoperative course was uneventful in general. At present, 17 months after LRLT, the patient shows stable liver function and no signs of either GVHD or a relapse of ALL. In conclusion, LRLT can be seen as a feasible option for the treatment of a hepatic VOD after CBT, though aggressive prophylaxis for infection and the anticipation of acute rejection are of importance.

Abstract:  Two methods were developed for the quantitative sampling of rotifers and cladocerans attached to aquatic macrophytes while separating them from plankton. We named them the “covering method” and the “picking-up method.” We consider the covering method to be better for estimating the abundance of animals on plants, but it requires hard work on a boat. In contrast, the picking-up method is simple and easy to perform, but it seems to estimate animal abundance with some errors. The densities of rotifers and cladocerans on emergent and submerged plants in two Japanese lakes were estimated by the two methods, and the results were compared. The densities of most animals (e.g., the rotiferans Brachionus, Mytilina, Lepadella, and Colurella, and the cladoceran Alona) estimated by the picking-up method did not differ from those estimated by the covering method. In contrast, the densities of the rotiferans Monostyla, Euchlanis, and Trichocerca estimated by the picking-up method tended to be lower than those estimated by the covering method. These suggest that the picking-up method is suitable for estimating many densities, except for some rotiferan genera.

OBJECTIVE: To explore the association between HLA genotypes and clinical and immunological characteristics in Caucasians with primary Sjögren's syndrome (pSS). METHODS: HLA genotyping for DRB1, DQA1 and DQB1 was carried out in 62 single case patients with pSS and 64 healthy controls. The specific amino acid residues at DQA1 position 34 (DQalpha-34Q) and DQB1 position 26 (DQbeta-26L) in addition to the DQ-DI (AA59-AA69) motif were deterrmined. Subsequently, the relative contribution of individual HLA markers to clinical and immunologic characteristics of pSS was assessed by group comparisons. RESULTS: No significant associations were seen between HLA markers and histopathological or clinical features of pSS. Significant positive associations with HLA Class II markers were restricted to the formation of different autoantibodies. Formation of an anti-Ro/SSA and anti-La/SSB autoantibody response was positively associated with DRB1*03, DQB1*02 and DRB1*03/DRB1*15-DQB1*02/DQB1*0602 heterozygosity. Patients positive for anti-La/SSB also showed a strong positive anti-La/SSB association with DQA1*0501. Considering the contribution of individual DQA1 and DQB1 amino acids and sequence motifs to the formation of anti-Ro/SSA and anti-La/SSB autoantibodies, a dose dependent positive influence was detected for DQalpha-34Q and DQbeta-26L. For DQbeta-DI, the largest difference between patients and controls was seen for the presence of a single copy of this motif after selecting patients with either anti-Ro/SSA or anti-La/SSB autoantibodies. CONCLUSION: The association of HLA Class II markers with pSS may concern the anti-Ro/La response rather than the disease itself. The strongest contributors to the formation of an anti-Ro/La response included components of the DRB1*03-DQB1*02-DQA1*0501 haplotype also encompassing the transethnically-associated DQbeta-DI motif. In addition, the dose dependent contribution of DQalpha-34Q and DQbeta-26L argue for a recessive contribution of HLA-DQ to the formation of an anti-Ro/La response. Given the prominent associations with DRB1*03 and the complex dose dependent interactions at HLA-DQ, a joint contribution of HLA-DR and DQ is likely to be relevant for the formation of anti-Ro/La autoantibodies in patients with pSS.

We have previously reported linkage of systemic lupus erythematosus to chromosome 2q37 in multicase families from Iceland and Sweden. This locus (SLEB2) was identified by linkage to the markers D2S125 and D2S140. In the present study we have analyzed additional microsatellite markers and SNPs covering a region of 30 cM around D2S125 in an extended set of Nordic families (Icelandic, Swedish, and Norwegian). Two-point linkage analysis in these families gave a maximum lod score at the position of markers D2S2585 and D2S2985 (Z= 4.51, PIC = 0.65), by applying a “model-free” pseudo-marker linkage analysis. Based on multipoint linkage analysis in the Nordic families, the most likely location of the SLEB2locus is estimated to be in the interval between D2S125 and the position of markers D2S2585 and D2S2985, with a peak multipoint lod score of Z= 6.03, assuming a dominant pseudo-marker model. Linkage disequilibrium (LD) analysis was performed using the data from the multicase families and 89 single-case families of Swedish origin, using the same set of markers. The LD analysis showed evidence for association in the single-case and multicase families with locus GAAT3C11 (P< 0.0003), and weak evidence for association was obtained for several markers located telomeric to D2S125 in the multicase families. Thirteen Mexican families were analyzed separately and found not to have linkage to this region. Our results support the presence of the SLEB2locus at 2q37.

The objective of our retrospective study was to clarify factors relating to place of death of Japanese people from a small town in a rural area who had been bedridden for at least one week before dying. The caregivers of subjects aged 40 and above who died during a three-year period were surveyed by trained interviewers. Of 352 subjects who died, 312 caregivers responded and agreed to a face-to-face interview. A total of 213 subjects were considered as an eligible sample. The main outcome measures were odds ratios for death at home in relation to age, pain, cause of death, and home visit service. One hundred and two people died at home, while 112 people died in a hospital. Multivariate logistic regression analysis showed that the probability of home death increased with age of the bedridden, lack of pain during the bedridden period, not having cancer as a cause of death, having senility as a cause of death, and receiving regular home visits by a Public Health Nurse. In conclusion, expansion of the home visit programs by Public Health Nurses may enable people to die at home as they so desire. Further prospective research is needed to explore the association between the attitude toward terminal care and the place of death.

Renal involvement was evaluated in 62 patients with primary Sjögren's syndrome, classified according to criteria proposed by The European Classification Criteria Group. Urine concentration capacity was tested using intranasal 1‐desamino‐8‐D‐arginine‐vasopressin. For patients with urine pH>5.5 without metabolic acidosis (n=28), an acidification test with ammonium chloride was performed. Urinary citrate, albumin, NAG, ALP and β2‐microglobulin were measured and creatinine clearance was calculated. Maximum urine concentration capacity and creatinine clearance were reduced in 13 (21%). Albumin excretion was >30 μg/min in only one patient (1.6%). Seven patients (11.3%) had complete or incomplete distal renal tubular acidosis (dRTA), four had reduced creatinine clearance and five had reduced maximum urine concentration capacity. The ratio of citrate/creatinine in spot urine was below the 2.5 percentile in all patients with complete or incomplete dRTA. The prevalence of dRTA was lower than in previous studies. There were also few patients with signs of glomerular disease (1.6%). The use of citrate:creatinine ratio in spot urine can be a helpful method in identifying patients with complete or incomplete dRTA.

AbstractTwo previous works[1,2]firstly evidenced the possible occurrence of gaps of miscibility in smectic A solutions of two non polymer mesogens and later demonstrated the connection of this phenomenon with the difference in layer spacing of the two pure components. In the present paper we provide a detailed thermal and structural analysis of the phase separation around the smecticA-smecticA consolute point of a selected system. It encompasses two high temperature resolution studies which give valuable information about the universality class to which this critical point is likely to be attached.

Objective. To study the association between disease activity and complement activation prospectively in patients with systemic lupus erythematosus (SLE).Patients and methods. Twenty-one SLE patients were examined monthly for 1 yr. Disease activity, autoantibodies, conventional complement tests and the following complement activation products were investigated: C1rs–C1inh complexes, C4bc, Bb, C3a, C3bc, C5a and the terminal SC5b–9 complement complex (TCC).Results. Modest variation in disease activity was noted. None of the patients had nephritis. Flare was observed at 27 visits. Four patients had anti-C1q antibodies in conjunction with modestly low C1q concentrations. The complement parameters were rather constant during the observation period. Slightly to moderately decreased C4 (0.05–0.10 g/l) was found in 10 patients and severely decreased C4 (<0.05 g/l) in seven patients. Decreased C4 was not associated with increased complement activation. Complement activation products were either normal or slightly elevated. TCC was the only activation product correlating significantly with score for disease activity at flare. None of the variables tested predicted flares.Conclusion. Complement tests are of limited importance in routine examination of SLE without nephritis, although TCC is suggested to be one of the most sensitive markers for disease activity.

We identified an amino acid transporter that is associated with the cystinuria-related type II membrane glycoprotein, rBAT (related to b(0,+) amino acid transporter). The transporter designated BAT1 (b(0, +)-type amino acid transporter 1) from rat kidney was found to be structurally related to recently identified amino acid transporters for system L, system y(+)L, and system x(-)C, which are linked, via a disulfide bond, to the other type II membrane glycoprotein, 4F2hc (4F2 heavy chain). In the nonreducing condition, a 125-kDa band, which seems to correspond to the heterodimeric complex of BAT1 and rBAT, was detected in rat kidney with anti-BAT1 antibody. The band was shifted to 41 kDa in the reducing condition, confirming that BAT1 and rBAT are linked via a disulfide bond. The BAT1 and rBAT proteins were shown to be colocalized in the apical membrane of the renal proximal tubules where massive cystine transport had been proposed. When expressed in COS-7 cells with rBAT, but not with 4F2hc, BAT1 exhibited a Na(+)-independent transport of cystine as well as basic and neutral amino acids with the properties of system b(0,+). The results from the present investigation were used to establish a family of amino acid transporters associated with type II membrane glycoproteins.

Defects in electron irradiated Cz-Si were studied by the positron annihilation technique. In order to know effects of the thermal history of crystals on the introduction of defects, the specimen was quenched from 1390°C to room temperature before irradiation. A clear correlation between results obtained by the positron annihilation experiments and those by infrared spectroscopy was established. From the isochronal annealing experiment, it was found that oxygen clusters were introduced by quenching treatments.

Background & Aims: The oligopeptide transport system of the small intestine is resistant to mucosal injury. The mechanism of this resistance was investigated by examining the activity level and expression of the peptide transporter PepT1 in the intestine of rats treated with 5-fluorouracil. Methods: The expression and localization of PepT1 were examined by immunoblot analysis of brush border membrane vesicles and immunohistochemical analysis of intestinal sections with PepT1-specific rabbit polyclonal antibodies. Also, Northern blot analysis was used for the expression of PepT1 messenger RNA (mRNA). Results: Although the amounts of sucrase and an Na^+-dependent glucose transporter protein in intestinal vesicles decreased markedly after 5-fluorouracil treatment, the amount of PepT1 protein remained largely unaffected. Immunohistochemical analysis also showed that the PepT1 immunoreactivity level was preserved in the brush border membrane of the remaining villi of 5-fluorouracil-treated rats. Levels of amino acid, glucose, and phosphate transporter mRNAs were profoundly depressed in 5-fluorouracil-treated animals, whereas the level of PepT1 mRNA conversely increased. Conclusions: The resistance of intestinal peptide transport to tissue injury may be attributable to increased synthesis of PepT1 rather than to a change in the kinetic properties of the residual absorbing cells. GASTROENTEROLOGY 1998;114:714-723

To determine the role of a neutral and basic amino acid transporter (NBAT) in amino acid transport, we microinjected several COOH-terminal deletion mutants of NBAT cRNA into Xenopus oocytes and measured transport activity for arginine, leucine, and cystine in the presence and absence of sodium. Wild-type NBAT significantly stimulated the uptake of all three amino acids 10-20-fold compared with controls. On the other hand, no mutant, except a Delta511-685 mutant, stimulated the uptake of these amino acids. The Delta511-685 mutant significantly increased the uptake of arginine. In the presence of sodium, the Delta511-685 mutant also increased the uptake of leucine. The Delta511-685 mutant did not stimulate cystine uptake in the presence or absence of sodium. The stimulation of arginine uptake by the Delta511-685 mutant was inhibited by a 100-fold excess of unlabeled leucine in the presence of sodium. Inhibition of L-arginine uptake by L-homoserine was seen only in the presence of sodium, and an increase in the inhibition of L-arginine uptake by L-histidine was seen when the extracellular pH was decreased. Furthermore, an inward current in oocytes injected with the Delta511-685 mutant was recorded electrophysiologically when basic amino acids were applied. Homoserine was also taken up, but sodium was necessary for their transport. These properties of the Delta511-685 mutant correspond to those of the y+ amino acid transporter. If NBAT is a component of the b0,+-like amino acid transport system, it is unlikely that a mutant protein (Delta511-685) is able to stimulate an endogenous y+-like transport system. These results suggest that NBAT functions as a activator of the amino acid transport system in Xenopus oocytes.

Inorganic salts, several proteins and traces of protein precipitants were tested to find out by what mechanisms they modulate the binding of cyclic [3H]AMP to protein kinase (ATP-protein phosphotransferase; EC 2.7.1.37). The separation of free and bound cyclic AMP by (NH4)2SO4 precipitation was unaffected by the above agents and was more reliable than the Millipore filtration technique. Several binding sites for cyclic AMP were revealed in adrenal-cortex extract. When this extract was used as binding reagent in an assay for cyclic AMP, the standard curve was distorted in the presence of KCl because the salt affected the different binding sites to a varying extent. At high ionic strenth the protein kinase isoenzyme I dissociated and showed an extraordinarily high affinity for cyclic AMP. Trichloroacetate and perchlorate at very low concentrations were able to dissociate the protein kinase and modulate its binding characteristics as well. A progressive decrease in the cyclic AMP-binding capacity occurred on prolonged incubations. The binding protein was protected against inactivation by 2-mercaptoethanol, EDTA and several proteins. It was more resistant to denaturation when complexed to cyclic AMP. The enhancement of cyclic AMP binding by bovine serum albumin was investigated in some detail and appeared to be a pure stabilizing effect. It is proposed that the competitive-binding assays for cyclic AMP based on protein kinase be conducted at high ionic strength and in the presence of stabilizers (protein, EDTA, 2-mercaptoethanol). The interference from agents that may dissociate the protein kinase or influence its stability will thus be decreased.

We investigated the effects of transfection of wild-type TP53on the growth properties of a human gingival carcinoma cell line, KOSC-3, in which the TP53gene is mutated at codon 248 and overexpressed. The wild-type TP53expression plasmid, pCDM8-p53/neo and the control plasmid, pCDM8/neo, were each stably transfected into KOSC-3 cells by using the calcium phosphate method. The number of G418-resistant colonics from wild-type TP53-transfected cells was approximately half that from plasmid controls. Exogenous wild-type TP53transcripts were identified in four of the 20 G418-resistant clones analysed by reverse transcription PCR. Although the growth rates of the wildtype TP53+clones did not drastically change during log phase, their saturation density was significantly reduced. The wild-type TP53+cells were morphologically flat and enlarged when cultured in vitro, and were less able to form colonics in soft agar. In nude mice, the wild-type TP53+clones formed subcutaneous tumours with conspicuous keratinisation and notable cell death that was not manifested in the parental and plasmid control cells. These findings indicate that the wild-type TP53gene, even when it coexists with a mutated form, may function as a growth suppressor and differentiation inducer under restricted conditions in gingival squamous cell carcinoma.

We review our experience with low-dose intravenous pulse cyclophosphamide as treatment of biopsy-proven lupus nephritis. Seventeen patients were treated with 2-4 (mostly 3) weekly low-dose intravenous pulses of cyclophosphamide (500 mg) and moderate doses of prednisolone (0.5mg/kg/day), followed by an oral immunosuppressive drug (either azathioprine or cyclophosphamide). As compared with the classical monthly high-dose cyclophosphamide regimen, this weekly low-dose regimen induced neutropenia in one patient only. The incidence of herpes zoster was very low (6 %). At the end of the follow-up period (15 ± 8 months), two patients required chronic ambulatory peritoneal dialysis. The 14 patients that could be evaluated improved their mean serum albumin from 30 ± 7 to 37.5 ±7 g/l (mean ± SD; P< 0.01) and their mean serum creatinine fell from 125 ± 119 to 101 ± 66 μmol/l (not significant). Mean DNA binding dropped from 71 ± 29 to 26 ± 27 % (P< 0.001) and mean complement fraction C4 levels increased from 14 ± 8 to 28 ± 18 mg/dl (P< 0.05). The mean daily prednisolone dose was dramatically reduced from 26 ± 8 to 10 ± 4 mg (P< 0.001). Although this preliminary and retrospective study clearly needs validation with a larger cohort followed for a longer period, it seems that a treatment combining moderate doses of steroids and 3-4 weekly low-dose intravenous pulses of cyclophosphamide, followed by oral immunosuppression, is well tolerated and beneficial — at least in the short term — for most patients with severe lupus nephritis.

The present paper examines the relationship of nutritional status to further life expectancy and health status in the Japanese elderly based on 3 epidemiological studies.Nutrient intakes in 94 Japanese centenarians investigated between 1972 and 1973 showed a higher proportion of animal protein to total proteins than in contemporary average Japanese. High intakes of milk and fats and oils had favorable effects on 10-year (1976–1986) survivorship in 422 urban residents aged 69–71. The survivors revealed a longitudinal increase in intakes of animal foods such as eggs, milk, fish and meat over the 10 years. Nutrient intakes were compared, based on 24-hour dietary records, between a sample from Okinawa Prefecture where life expectancies at birth and 65 were the longest in Japan, and a sample from Akita Prefecture where the life expectancies were much shorter. Intakes of Ca, Fe, vitamins A, B1, B2, C, and the proportion of energy from proteins and fats were significantly higher in the former than in the latter. Intakes of carbohydrates and NaCl were lower.

An assay for cyclic AMP is described which takes advantage of the high affinity of the dissociated receptor moiety of cyclic AMP-dependent protein kinase I for the nucleotide. The kinase is kept dissociated by salt (800 mM-NaCl/30mM-EDTA). In the presence of a simply prepared heat-stable protein fraction the binding reagent is stable for the time needed to reach equilibrium of binding. A simple procedure [precipitation with poly-(ethylene glycol) followed by DEAE-cellulose chromatography] is described for the separation of protein kinase I from other binding proteins for cyclic AMP in rabbit skeletal muscle. The sensitivity, precision, reproducibility and specificity of the assay compared favourably with those of other cyclic AMP assays. The main advantage of the present assay is its resistance towards non-specific interference from a number of salts, tissue-culture media and substances found in crude tissue extracts. The reliability of cyclic AMP measurement directly in crude tissue extracts was ensured by removal of the assayable cyclic AMP with cyclic nucleotide phosphodiesterase digestion or adsorption with antibody against cyclic AMP, by comparison with measurement in tissue extracts purified by chromatography on QAE-Sephadex or sequentially on Dowex 50, and aluminium oxide as well as by dilution and recovery experiments.

Highly sensitive techniques have been used for the assay of a range of marker enzymes including lactase, sucrase, alkaline phosphatase, leucyl-β-naphthylamidase (brush border), and 5′-nucleotidase (basolateral membrane) in jejunal biopsy homogenates from patients with adult coeliac disease with and without steatorrhoea and from a control group. The absorption of D-xylose and vitamin B12was compared in the two groups with coeliac disease. All enzymes assayed were equally depressed in both groups of coeliac disease as compared with the controls. The absorption of D-xylose and vitamin B12were reduced in the patients with steatorrhoea compared with those without steatorrhoea. The findings suggest that lack of steatorrhoea in some patients with coeliac disease is due to better preservation of the ileal function rather than to a less severe jejunal mucosal injury.

Summary A 500 mg intramuscular dose of carbenicillin produced peak levels averaging 147µg/ml after three hours in the first day full-term newborn infants, and 172µg/ml after one to two hours in infants five days of age. The fall of blood levels thereafter was delayed and serum half-life averaged 4.2 and 2.2 hours in both groups, almost four times and twice as long, respectively, as that reported in adults. Absorption from the injected site was also delayed in young newborns, as was shown by the delayed serum peak and small estimated absorption rate constant. This must be taken into consideration if the intramuscular route is chosen in young newborn infants. On the basis of serum half-life, an administration interval of 12 hours was recommended for newborns younger than four days, and eight hours for those five days of age or more.

The prevalence of thyroid antibodies in 100 patients with rheumatoid arthritis in Northern Norway was studied. The serological data were compared with those from a major population survey in the same area. Compared to the prevalence in the normal population, the present study demonstrates that patients with rheumatoid arthritis have a higher prevalence of antibodies to both thyroid microsomal antigen and thyroglobulin.

We measured the static friction force of agar gel-on-glass plate in water. The static friction force is independent of the apparent contact area between the agar gel and the glass plate. It increases with waiting time, that is, contact duration prior to motion. The static friction force is represented well by a power law of waiting time. The waiting time dependence is different from those of solid-on-solid systems. These results are discussed, based on asperity contact model.

We carried out a prospective study of the prevalence and characteristics of anticardiolipin antibodies aCL and migraine on 103 consecutive patients with systemic lupus erythematosus SLE derived from three European referral university centers. We also included a control group of 58 patients with migraine not associated with SLE. We interviewed all patients using a data collection form designed to provide a complete record of the clinical characteristics of headache. Fiftyfour 52 patients with SLE suffered recurrent headache. We diagnosed migraine in 32 patients, tension headache in 21, and cluster headache in one. Thirty 29 patients with SLE had aCL. Migraine was present in five patients with aCL and in 27 patients without aCL 17 versus 37, p0.07. No migraine control patient had aCL. Our study highlights the frequency of headache in SLE, but does not support an association between the presence of aCL and migraine in this disease.

The image tube streak camera was applied to the observation of fast modulated continuous light signals. Intensity modulation of a semiconductor laser was observed up to 5 GHz.