Bullous pemphigoid arising in a patient with acquired perforating dermatosis.

A middle-aged Japanese man who had been on haemodialysis treatment for diabetic nephropathy developed multiple itchy papules and nodules, which were histopathologically diagnosed as acquired perforating dermatosis. Two years later he developed oral lesions and subsequently numerous erosive plaques with necrotic crusts on the trunk and extremities. Histopathology of a papule showed a parakeratotic plug intermingled with basophilic, necrotic debris and collagen bundles, along with penetration of collagen bundles across the epidermis and subepidermal blister. Immunoblotting studies revealed IgG autoantibodies in the patient's serum, which reacted with the C-terminal and the NC16a domains of bullous pemphigoid (BP)180, indicating presence of BP. We searched the literature and found no other cases of an autoimmune blistering disease occurring in association with a perforating disorder. Possible injury to the basement membrane zone induced during the process of transepidermal elimination might be involved in the pathogenesis of the pemphigoid disease.

Characterization and gene cloning of a maltotriose-forming exo-amylase from Kitasatospora sp. MK-1785.

A maltotriose-forming amylase (G3Amy) from Kitasatospora sp. MK-1785 was successfully isolated from a soil sample by inhibiting typical extracellular α-amylases using a proteinaceous α-amylase inhibitor. G3Amy was purified from the MK-1785 culture supernatant and characterized. G3Amy produced maltotriose as the principal product from starch and was categorized as an exo-α-amylase. G3Amy could also transfer maltotriose to phenolic and alcoholic compounds. Therefore, G3Amy can be useful for not only maltotriose manufacture but also maltooligosaccharide-glycoside synthesis. Further, the G3Amy gene was cloned and expressed in Escherichia coli cells. Analysis of its deduced amino acid sequence revealed that G3Amy consisted of an N-terminal GH13 catalytic domain and two C-terminal repeat starch-binding domains belonging to CBM20. It is suggested that natural G3Amy was subjected to proteolysis at N-terminal region of the anterior CBM20 in the C-terminal region. As with natural G3Amy, recombinant G3Amy could produce and transfer maltotriose from starch.

Time-, spin-, and angle-resolved photoemission spectroscopy with a 1-MHz 10.7-eV pulse laser.

We describe a setup of time-, spin-, and angle-resolved photoemission spectroscopy (tr-SARPES) employing a 10.7 eV (λ = 115.6 nm) pulse laser at a 1 MHz repetition rate as a probe photon source. This equipment effectively combines the technologies of a high-power Yb:fiber laser, ultraviolet-driven harmonic generation in Xe gas, and a SARPES apparatus equipped with very-low-energy-electron-diffraction spin detectors. A high repetition rate (1 MHz) of the probe laser allows experiments with the photoemission space-charge effects significantly reduced, despite a high flux of 1013 photons/s on the sample. The relatively high photon energy (10.7 eV) also brings the capability of observing a wide momentum range that covers the entire Brillouin zone of many materials while ensuring high momentum resolution. The experimental setup overcomes the low efficiency of spin-resolved measurements, which gets even more severe for the pump-probed unoccupied states, and affords the opportunity to investigate ultrafast electron and spin dynamics of modern quantum materials with energy and time resolutions of 25 meV and 360 fs, respectively.

Coverage and Cost-of-Care Links: Addressing Financial Toxicity Among Patients With Hematologic Cancer and Their Caregivers.

PURPOSE: This study examined the feasibility, acceptability, and preliminary effectiveness of an oncology financial navigation (OFN) intervention, Coverage and Cost-of-Care Links (CC Links), among patients with hematologic cancer and their caregivers who are at increased risk of experiencing financial toxicity (FT). METHODS: All patients who presented to the Division of Hematology and Bone and Marrow Transplant (BMT) at an National Cancer Institute-designated cancer center between April 2021 and January 2022 were screened for FT during inpatient and outpatient visits. Patients who screened positive for FT and met the inclusion criteria were recruited to participate in CC Links that provided financial navigation and assistance via a financial navigator. Caregivers of patients undergoing BMTs were also recruited to participate. Primary outcomes were defined as improvements in FT, distress, and physical and mental quality of life. RESULTS: Fifty-four patients and 32 caregivers completed the intervention and pre-/postintervention surveys. CC Links resulted in statistically significant decreases in the Comprehensive Score for FT for both patients (|t| = 2.42, P = .019) and caregivers (|t| = 2.43, P = .021) and total FT (|t| = 2.13, P = .041) and material conditions scores (|t| = 2.25, P = .031) for caregivers only. Only 27% of eligible patients participated in the study, whereas 100% of eligible caregivers participated. The majority of participants rated the intervention highly for acceptability (89%) and appropriateness (88%). An average of $2,500 (USD) in financial benefits was secured per participant via CC Links. CONCLUSION: CC Links was effective in decreasing FT among patients with hematologic cancer and their caregivers while demonstrating high acceptability and appropriateness ratings.

Transfer of orbital angular momentum of light to plasmonic excitations in metamaterials.

The emergence of the vortex beam with orbital angular momentum (OAM) has provided intriguing possibilities to induce optical transitions beyond the framework of the electric dipole interaction. The uniqueness stems from the OAM transfer from light to material, as demonstrated in electronic transitions in atomic systems. In this study, we report on the OAM transfer to electrons in solid-state systems, which has been elusive to date. Using metamaterials (periodically textured metallic disks), we show that multipolar modes of the surface electromagnetic excitations (so-called spoof localized surface plasmons) are selectively induced by the terahertz vortex beam. Our results reveal selection rules governed by the conservation of the total angular momentum, which is confirmed by numerical simulations. The efficient transfer of light's OAM to elementary excitations in solid-state systems at room temperature opens up new possibilities of OAM manipulation.

Predictors of Cerebral Aneurysm Rupture after Coil Embolization: Single-Center Experience with Recanalized Aneurysms.

BACKGROUND AND PURPOSE: Recanalization after coil embolization is widely studied. However, there are limited data on how recanalized aneurysms rupture. Herein, we describe our experience with the rupture of recanalized aneurysms and discuss the type of recanalized aneurysms at greatest rupture risk. MATERIALS AND METHODS: A total of 426 unruptured aneurysms and 169 ruptured aneurysms underwent coil embolization in our institution between January 2009 and December 2017. Recanalization occurred in 38 (8.9%) of 426 unruptured aneurysms (unruptured group) and 37 (21.9%) of 169 ruptured aneurysms (ruptured group). The Modified Raymond-Roy classification on DSA was used to categorize the recanalization type. Follow-up DSA was scheduled until 6 months after treatment, and follow-up MRA was scheduled yearly. If recanalization was suspected on MRA, DSA was performed. RESULTS: In the unruptured group, the median follow-up term was 74.0 months. Retreatment for recanalization was performed in 18 aneurysms. Four of 20 untreated recanalized aneurysms (0.94% of total coiled aneurysms) ruptured. In untreated recanalized aneurysms, class IIIb aneurysms ruptured significantly more frequently than class II and IIIa (P = .025). In the ruptured group, the median follow-up term was 28.0 months. Retreatment for recanalization was performed in 16 aneurysms. Four of 21 untreated recanalized aneurysms (2.37% of total coiled aneurysms) ruptured. Class IIIb aneurysms ruptured significantly more frequently than class II and IIIa (P = .02). CONCLUSIONS: The types of recanalization after coil embolization may be predictors of rupture. Coiled aneurysms with class IIIb recanalization should undergo early retreatment because of an increased rupture risk.

High speed clinical data retrieval system with event time sequence feature: with 10 years of clinical data of Hamamatsu University Hospital CPOE.

OBJECTIVES: This paper illustrates a high speed clinical data retrieving system, from 10 years of data of operating hospital information system for the purposes of research, evidence creation, patient safety, etc., even incorporating time sequence of causal relations. METHODS: Total of 73,709,298 records of 10 years at Hamamatsu University Hospital (as of June 2008) are sent from HIS to retrieval system in HL7 v2.5 format. Hierarchical variable length database is used to install them. RESULTS: A search for "listing patients who were prescribed Pravastatin (Mevalotin and generic drugs, any titer)" took 1.92 seconds. "Pravastatin (any) prescribed and recorded AST >150 within two weeks" took 112.22 seconds. Searching conditions can be set to be more complex, connected by Boolean operator and/or. This system called D*D is in operation at Hamamatsu University Hospital since August 2002. It is used for 48,518 times (monthly average of 703 searches). Neither searching, nor background export of data from HIS caused delay of routine operating CPOE. CONCLUSIONS: Search database outside of routine operating CPOE, with daily export of order data in HL7 v2.5 format, is proved to provide excellent search environment without causing trouble. Hierarchical representation gives high-speed search response, especially with time sequence of events.

High incidence of autoimmune gastritis in patients misdiagnosed with two or more failures of H. pylori eradication.

BACKGROUND: Although autoimmune gastritis (AIG) is generally considered relatively rare, we frequently encounter AIG among patients at to our hospital who have experienced at least two episodes of Helicobacter pylori eradication failure. AIMS: We investigated the incidence of AIG in consecutive patients who consulted our department for H. pylori eradication with reference to eradication history. METHODS: A total of 404 consecutive patients who visited the H. pylori-specific out-patient unit of our hospital from June 2015 to June 2017 were enrolled. Of these, 137 were treatment-naive, 47 had failed treatment once (single failure), and 220 had failed treatment twice or more (multiple failures) by 13 C-UBT. Gastroscopy was performed in all patients. Culture tests of gastric mucosal samples were performed for H. pylori and other bacteria positive for urease activity. Anti-parietal cell antibody (APCA) was measured. Patients with severe atrophy in the gastric corpus and positivity for APCA were diagnosed as having AIG. RESULTS: A total of 43 patients were diagnosed as having AIG, of whom two were treatment-naive (1.5%, 2/137), 1 failed eradication once (2.1% 1/47), and 40 failed treatment at least twice (18.2%, 40/220). The incidence of AIG was significantly higher in the multiple failure group than in the single failure or treatment-naive groups. Urease-positive bacteria, such as Klebsiella pneumoniae and alpha-streptococcus, were identified in 33 of the 35 AIG patients who underwent culture testing. CONCLUSION: AIG patients were often misdiagnosed as refractory to eradication therapy, probably because achlorhydria in AIG might allow urease-positive bacteria other than H. pylori to colonise the stomach, causing positive 13 C-UBT results.

[Characteristics of Low-Level Persistent viraemias in HIV-1 Patients Treated with Second-Line ARVs at the Sourô Sanou Teaching Hospital of Bobo-Dioulasso (Burkina Faso)]. / Caractéristiques des virémies persistantes de bas niveau des patients VIH-1 sous traitement antirétroviral de deuxième ligne au CHU Sourô Sanou de Bobo-Dioulasso (Burkina Faso).

We describe the characteristics of patients infected with HIV-1 as second-line antiretroviral therapy, with persisting low-level viremia. This was a descriptive retrospective study, conducted from January 1, 2010 to December 31, 2016, from the Cohort of the Infectious Diseases Department of Bobo-Dioulasso University Hospital. Patients infected with HIV-1, a second line of stable ARV treatment, with ≥95% compliance for at least 12 months, asymptomatic with CVp between 50 and 1000 copies/ml in two consecutive samplings at least 3 months apart. Out of 244 patients in second-line therapy, 79 met our inclusion criteria. The mean age of the patients was 42±10.2 years. Women (35.8 years) were younger than men (43.8 years) (p=0.001). Most were married (48.1%), 23.5% of whom were polygamous. The majority of patients (38/79) in the study had a CD4 count of <200 cells/ mm3. The median duration of ARV therapy since the beginning of the therapeutic history has been 4.8 (2.5-11 years). CVp greater than 10,000 copies/ml at the start of second-line therapy (p=0.003) and TDF+FTC + DRV + RTV combination (p=0.001) were associated with persistent low viremia. A genotypic resistance test is needed for these patients in order to better adapt the ARV treatment.

Nous décrivons les caractéristiques des patients infectés par le VIH-1 en deuxième ligne de traitement antirétroviral, avec une virémie persistante de bas niveau. Il s'agissait d'une étude rétrospective à visée descriptive, menée du 1er janvier 2010 au 31 décembre 2016, à partir de la cohorte du service des maladies infectieuses du CHU de Bobo-Dioulasso. Ont été inclus les patients infectés par le VIH-1, en deuxième ligne de traitement ARV stable, ayant une observance ≥ 95 % depuis au moins 12 mois, asymptomatiques, avec une charge virale plasmatique comprise entre 50 et 1 000 copies/ml sur deux prélèvements consécutifs à au moins 3 mois d'intervalle. Sur 244 patients en deuxième ligne de traitement antirétroviral, 79 répondaient à nos critères d'inclusion. L'âge moyen des patients était de 42 ± 10,2 ans. Les femmes (35,8 ans) étaient moins âgées que les hommes (43,8 ans) (p = 0,001). La plupart des patients étaient mariés (48,1 %), parmis lesquels certains vivaient dans des régimes polygames (23,5 %). La majorité des patients (38/79) de l'étude avaient un taux de CD4 ≤ 200 cellules/mm3. La durée médiane du traitement ARV depuis le début de l'histoire thérapeutique était de 4,8 ans (2,5- 11 ans). La charge virale plasmatique supérieure à 10 000 copies/ml au début du traitement (p = 0,003), et la combinaison TDF+FTC+DRV+RTV (p = 0,001) étaient associées à la virémie persistante de bas niveau. La réalisation d'un test génotypique de résistance s'impose pour ces patients afin de mieux adapter le traitement antirétroviral.

The N- and C-terminal regions of RBP-J interact with the ankyrin repeats of Notch1 RAMIC to activate transcription.

The evolutionarily-conserved DNA-binding protein RBP-J directly interacts with the RAM domain and the ankyrin (ANK) repeats of the Notch intracellular region (RAMIC), and activates transcription of downstream target genes that regulate cell differentiation. In vitro binding assays demonstrate that the truncated N- and C-terminal regions of RBP-J bind to the ANK repeats but not to the RAM domain. Using an OT11 mouse cell line, in which the RBP-J locus is disrupted, we showed that RBP-J constructs mutated in the N- and C-terminal regions were defective in their transcriptional activation induced by either RAMIC or IC (the Notch intracellular region without the RAM domain) although they had normal levels of binding activity to DNA and the RAM domain. The studies using chimeric molecules between RBP-J and its homolog RBP-L showed that the N- and C-terminal regions of RBP-J conferred the IC- as well as RAMIC-induced transactivation potential on RBP-L, which binds to the same DNA sequence as RBP-J but fails to interact with RAMIC. Taken together, these results indicate that the interactions between the N- and C-terminal regions of RBP-J and the ANK repeats of RAMIC are important for transactivation of RBP-J by RAMIC.

Background values for evaluation of heavy metal contamination in sediments.

The contamination of sediments can be evaluated from comparison of the current concentration with the estimated background value. Although it is known that grain size affects background concentrations, there have been difficulties in evaluating this effect. The specific surface area of sediments, which can be calculated from the grain size distribution, is introduced as a property index for correlation of background values. The results show that for sandy-to-sandy silt sediments, the background values of metals are expressed in terms of fines content, which can be correlated with the corresponding specific surface area. However, for silty clay or clayey silt sediments, which would have a high metal retention capacity, the level of the background may be constrained by the relatively low concentrations of metals in seawater. Finally, background levels of Zn, Cu and Pb are presented.

Restoration by adrenalectomy of weight and binding capacity of glucorcorticoid receptors of the thymus in AH 130 tumor-bearing rats.

The binding capacity of specific receptors for dexamethasone (11beta,17alpha,21-trihydroxy-9alpha-fluoro-16alpha-methyl-1,4-pregnadiene-3,20-dione) in the cytoplasm of the thymus of rats bearing AH 130 (solid-type) tumors decreased significantly during tumor growth. Adrenalectomy restored the binding capacity of the glucocorticoid receptors and the weight of the thymus to nearly the normal values in rats bearing tumors. The affinity of these receptors for dexamethasone was very low in rats bearing tumors, but it was also restored to nearly the normal value by adrenalectomy.

Aminotransferase activities and involution of the thymus in rats bearing AH 130 tumors.

Involution of the thymus was observed in rats bearing AH 130 (solid-type) tumors. The thymus weight decreased with tumor growth. Daily injection of a pharmacological dose of hydrocortisone into normal rats resulted in involution of the thymus and marked increase in alanine aminotransferase activity. This treatment also caused slight increase in the activity of tyrosine aminotransferase but not of aspartate aminotransferase in these animals. Involution of the thymus in tumor-bearing rats, however, was not accompanied by appreciable increases in the activities of these aminotransferases, even at an advanced stage of tumor growth when the plasma corticosterone level was very high and significant increase in the activities of all these enzymes was observed in the liver. Further, additional injections of hydrocortisone into rats with tumors weighing more than 5% of the body weight did not cause any appreciable change in alanine aminotransferase activity in the thymus, although in rats with smaller tumors it slightly increased the enzyme activity in the thymus. Furthermore, in normal rats, increase in alanine aminotransferase activity in the thymus with involution of the glands was observed with a dose of corticosterone close to the physiological range attained in rats with tumors in an advanced stage.

Recurrence patterns and factors associated with regular, irregular, and late return to service of female pigs and their lifetime performance on southern European farms.

A return-to-service occurrence increases nonproductive days of female pigs and decreases herd productivity. The objectives of the present study were 1) to characterize 3 return types based on reservice intervals in female pigs on southern European farms, 2) to determine return risks and recurrence patterns for these types of returns, and 3) to assess lifetime performance of females with the 3 types of returns. We analyzed 653,528 service records and lifetime records of 114,906 females on 125 farms between 2008 and 2013. Reservice intervals were categorized into 3 groups: regular returns (RR: 18 to 24 d), irregular returns (IR: 25 to 38 d), and late returns (LR: 39 d or later). Multilevel generalized linear models were applied to the data. There were 64,385 reservice records (9.9%), with mean risks of RR, IR, and LR per service (±SEM) of 3.6% ± 0.06%, 2.5% ± 0.05%, and 3.0% ± 0.06%, respectively. Of the 43,931 first-returned females, 32.7% had a second return in the same or later parity. Also, 18.8%, 10.2%, and 11.6% of females that had RR, IR, and LR first returns, respectively, had a second return of the same return type. Summer servicing was associated with greater RR, IR, and LR risks in gilts. Also, increased gilt age at first mating was associated with RR ( = 0.03) and LR risk ( < 0.01) but not with IR risk ( = 0.53). For sows, factors associated with greater RR, IR, or LR risks were summer servicing, lower parity, farrowing more stillborn piglets, and having a weaning-to-first-mating interval of 7 d or more ( < 0.01). In lifetime, 33.5% of serviced females had 1 or more returns. These returned females had 41.5 more lifetime nonproductive days than nonreturn females but also 1.9 more lifetime pigs born alive ( < 0.01). We recommend that producers closely monitor females in high-risk groups to reduce their return-to-service intervals.

Differences between Mitiglinide/Voglibose Fixed-dose Combination and Glimepiride in Modifying Low-density Lipoprotein Heterogeneity in Japanese Type-2 Diabetic Patients: A Pilot Study.

PURPOSE: The purpose of this study was to compare the effects of mitiglinide/voglibose fixed-dose combination and glimepiride on low-density lipoprotein (LDL)-heterogeneity in type-2 diabetic patients with unstable glycemic control after treatment with dipeptidyl peptidase-4 (DPP-4) inhibitors. METHODS: This was an open-label pilot study in which type-2 diabetic patients were randomly assigned to the mitiglinide/voglibose (fixed-dose combination of mitiglinide 10 mg and voglibose 0.2 mg, n=14) or glimepiride (0.5 mg, n=16). RESULTS: In the glimepiride group, serum LDL cholesterol (LDL-C) and small-dense (sd) LDL levels decreased significantly (-8.5% and -9.0%), while sd-LDL/LDL-C and an indicator of LDL-particle size, LDL-C/apoB, did not change significantly. In the mitiglinide/voglibose group, serum LDL-C levels did not change, while sd-LDL levels and sd-LDL/LDL-C decreased significantly (-8.6% and -7.9%) and LDL-C/apoB increased significantly (5.8%). Fasting blood glucose levels tended to be reduced to a greater extent in the glimepiride group than in the mitiglinide/voglibose group (-13.9% vs. -8.4%, p=0.08), while the rate of reduction of HbA1c levels tended to be higher in the mitiglinide/voglibose group than in the glimepiride group (-6.9% vs. -3.4%, p=0.09), suggesting differences in fluctuating blood glucose levels between the 2 groups. CONCLUSION: There were differences in the effects of mitiglinide/voglibose fixed-dose combination and glimepiride in addition to DPP-4 inhibitors on LDL-metabolism, and this may be related to fluctuations in blood glucose levels after treatment with these agents.

High repetition pump-and-probe photoemission spectroscopy based on a compact fiber laser system.

The paper describes a time-resolved photoemission (TRPES) apparatus equipped with a Yb-doped fiber laser system delivering 1.2-eV pump and 5.9-eV probe pulses at the repetition rate of 95 MHz. Time and energy resolutions are 11.3 meV and ∼310 fs, respectively, the latter is estimated by performing TRPES on a highly oriented pyrolytic graphite (HOPG). The high repetition rate is suited for achieving high signal-to-noise ratio in TRPES spectra, thereby facilitating investigations of ultrafast electronic dynamics in the low pump fluence (p) region. TRPES of polycrystalline bismuth (Bi) at p as low as 30 nJ/mm2 is demonstrated. The laser source is compact and is docked to an existing TRPES apparatus based on a 250-kHz Ti:sapphire laser system. The 95-MHz system is less prone to space-charge broadening effects compared to the 250-kHz system, which we explicitly show in a systematic probe-power dependency of the Fermi cutoff of polycrystalline gold. We also describe that the TRPES response of an oriented Bi(111)/HOPG sample is useful for fine-tuning the spatial overlap of the pump and probe beams even when p is as low as 30 nJ/mm2.

Debris-flow risk analysis in a managed torrent based on a stochastic life-cycle performance.

Two key factors can affect the functional ability of protection structures in mountains torrents, namely (i) infrastructure maintenance of existing infrastructures (as a majority of existing works is in the second half of their life cycle), and (ii) changes in debris-flow activity as a result of ongoing and expected future climatic changes. Here, we explore the applicability of a stochastic life-cycle performance to assess debris-flow risk in the heavily managed Wartschenbach torrent (Lienz region, Austria) and to quantify associated, expected economic losses. We do so by considering maintenance costs to restore infrastructure in the aftermath of debris-flow events as well as by assessing the probability of check dam failure (e.g., as a result of overload). Our analysis comprises two different management strategies as well as three scenarios defining future changes in debris-flow activity resulting from climatic changes. At the study site, an average debris-flow frequency of 21 events per decade was observed for the period 1950-2000; activity at the site is projected to change by +38% to -33%, according to the climate scenario used. Comparison of the different management alternatives suggests that the current mitigation strategy will allow to reduce expected damage to infrastructure and population almost fully (89%). However, to guarantee a comparable level of safety, maintenance costs is expected to increase by 57-63%, with an increase of maintenance costs by ca. 50% for each intervention. Our analysis therefore also highlights the importance of taking maintenance costs into account for risk assessments realized in managed torrent systems, as they result both from progressive and event-related deteriorations. We conclude that the stochastic life-cycle performance adopted in this study represents indeed an integrated approach to assess the long-term effects and costs of prevention structures in managed torrents.

Glyprolines exert protective and repair-promoting effects in the rat stomach: potential role of the cytokine GRO/CINC-1.

Glyprolines have been reported to exert protective effects in the stomach. In this study, we examined the potential effects of intranasal administration of Pro-Gly-Pro (PGP) and N-acetyl-Pro-Gly-Pro (AcPGP) on experimental gastric ulcer formation and healing. We also studied gastric release of the cytokine GRO/CINC-1, and its potential role in ulcer development and healing. Gastric ulcers were induced in rats by applying acetic acid to the serosa of the stomach. PGP and AcPGP were then administered at a dose of 3.7 µmol/kg once daily on either days 1 - 3 (ulcer formation) or days 4 - 6 (ulcer healing). Measurement of ulcer area and histological examination of gastric tissue were carried out on days 4 and 7 after application of acetic acid. In vitro studies involved addition of the glyprolines to cultured rat gastric epithelial cells with or without lipopolysaccharide. Reverse transcription PCR, real-time PCR and ELISA were used for cytokine analysis. PGP and AcPGP significantly reduced ulcer areas on the 4(th) day and accelerated the healing on the 7(th) day compared with the control. After acetic acid-induced ulceration, the expression of GRO/CINC-1 mRNA in gastric tissue was increased 9-fold versus the sham-operated group. Treatment with PGP or AcPGP both significantly suppressed the expression of GRO/CINC-1 mRNA in gastric tissue. However, the glyprolines did not alter LPS-induced mRNA expression or release of GRO/CINC-1 from cultured rat gastric epithelial cells, even though those cells were harvested from rats subjected to the ulcer-induction procedure. The results of this study show that intranasal administration of PGP and AcPGP significantly increased resistance against acetic acid-induced ulceration and accelerated healing in the rats. These effects may be due, at least in part, to their ability to reduce the acetic acid-induced GRO/CINC-1 expression and production in gastric tissue.

A comparative study of two kinds of cathepsin D-type proteinases from rat gastric mucosa.

The localization of cathepsin D-like acid proteinase in the rat stomach and other tissues was studied, and its biochemical properties were compared with those of rat gastric cathepsin D (EC 3.4.23.5). Cathepsin D-like acid proteinase existed overwhelmingly in the mucosal layer and was hardly detected in the gastric juice. Its subcellular distribution profile was very similar to that of acid phosphatase, but not to that of pepsinogen. This proteinase-like enzyme activity was also found in rat splenic extract. These results strongly suggest that the proteinase is a lysosomal enzyme. In addition, cathepsin D-like acid proteinase demonstrated an in vitro transition of molecular species during storage at -30 degrees C. Although this molecular change was distinctive in ion-exchange column chromatography and susceptibility to some enzyme inhibitors, it was not accompanied by a significant decrease in molecular weight. To compare cathepsin D-like acid proteinase with ordinary cathepsin D, gastric cathepsin D was newly purified to apparent homogeneity in polyacrylamide gel electrophoresis. Its biochemical properties demonstrate that this is a true cathepsin D in rat gastric mucosa. Moreover, this cathepsin D activity was not abolished by treatment with antiserum specific to cathepsin D-like acid proteinase or pepsinogen. From these results, we can conclude that the proteinase is a lysosomal acid proteinase different from newly purified gastric cathepsin D.

Purification and properties of a cathepsin D-like acid proteinase from rat gastric mucosa.

A unique acid proteinase was purified from rat gastric mucosa by DEAE-Sepharose CL-6B chromatography, gel filtration and isoelectric focusing. The purified enzyme was homogeneous by polyacrylamide disc gel electrophoresis. The molecular weight of the enzyme was estimated to be 86000 by gel filtration on a Sephadex G-100 column. In SDS-polyacrylamide gel electrophoresis, the enzyme showed a single band corresponding to a molecular weight of 42000. So it was concluded that the native enzyme is composed of two identical monomeric units. The enzyme is a glycoprotein and its isoelectric point was determined to be 4.33. The enzyme hydrolyzed bovine hemoglobin with maximum activity at pH 3.0, but it showed considerably lower activity on bovine serum albumin or casein than on bovine hemoglobin. The enzyme was strongly inhibited by pepstatin, but not by urea or thiol-reactive inhibitors. These results lead us to conclude that this enzyme is a cathepsin D-like acid proteinase.