Epithelioid granuloma formation requiring no T-cell function.

Muramyl dipeptide (MDP), a minimal structure in bacterial cell walls essential for their adjuvant activity, was incorporated in a water-in-oil emulsion and injected into the footpads of nude rats devoid of functional T cells. MDP thus injected evoked massive epithelioid granulomas in the draining lymph nodes, indicating that MDP induced epithelioid granuloma formation requires no T cells. This finding with other data available strongly suggest that epithelioid granulomas can be induced without immunologic reactions.     

Alpha 2-adrenergic modulation of pancreatic glucagon secretion in rats.

The present study was designed to clarify the mechanism of adrenergic modulation of pancreatic glucagon secretion in rats under physiological conditions by 1) epinephrine infusion alone or together with adrenergic blockers and 2) administration of adrenergic agonists. Intravenous infusion of epinephrine alone (1 microgram/kg/min, equal to 0.7 nmol/kg/min) caused a significant increase in glucagon secretion. Phentolamine (an alpha blocker) or yohimbine (an alpha 2 blocker) administration completely inhibited the increase of glucagon secretion caused by epinephrine infusion, but neither the administration of bunazosin (an alpha 1 blocker) nor beta blockers inhibited it. Infusion of clonidine (an alpha 2 agonist) caused significant increase of glucagon secretion even at a low dose of 0.5 nmol/kg/min, although infusion of neither an alpha 1 nor a beta 2 agonist caused it even at the high dose of 40.0 nmol/kg/min. It is concluded that the alpha 2 receptor mechanism plays the most important role in the adrenergic modulation of glucagon secretion in rats under physiological conditions.     

Differentiation of fibrinolysis and fibrinogenolysis by analysis of FDP fragments]

We previously analysed the fragments of fibrin/fibrinogen degradation products (FDP) by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) combined with immunoblotting. In this report, we studied the semi-quantitative analysis of fibrinolysis (degradation of cross-linked fibrin) and fibrinogenolysis (degradation of fibrinogen and/or unstable fibrin) of patients' samples by our method. In vitro study of FDP made it clear that an appearance of D fragment confirmed fibrinogenolysis and an appearance of DD fragment and/or high molecular weight fragments which have higher molecular weight than DY or X fragment confirmed fibrinolysis. In addition, a study with mixtures of various concentrations of fibrin degradation products (FbDP) and fibrinogen degradation products (FgDP) demonstrated a dose dependent intensity of band by immunoblot method. These results show that our method is favorable for the semi-quantitative analysis of fibrinolysis and fibrinogenolysis. We applied the method to 6 samples from patients with disseminated intravascular coagulation (DIC). Consequently, fibrinogenolysis was observed in all of 6 samples, in which fibrinogenolysis was more enhanced than fibrinolysis in one sample, and an equivalent degree of fibrinolysis and fibrinogenolysis were observed in 3 of 6 samples. Although our method was probably devoid of the ability to distinguish FgDP from degradation products of unstable fibrin, these findings indicate that fibrinogenolysis is, at any rate, enhanced in the majority of patients with DIC, besides fibrinolysis.     

Characterization of DNA sequences constituting the terminal heterochromatin of the chicken Z chromosome

Two clones, pCZTH5-8 and pCZTH12-8, were isolated from a female chicken genomic library by screening with sequences obtained from genomic libraries which had been constructed from a terminal region of a single Z chromosome of chicken utilizing laser microbeam irradiation and PCR amplification. Fluorescencein situ hybridization to the mitotic Z chromosome and the lampbrush ZW bivalent of chicken demonstrated that both the cloned sequences are located in the heterochromatic region of the Z chromosome at the end opposite to the pairing region with the W chromosome. The sequences pCZTH5-8 and pCZTH12-8 are distributed widely on both the telomeric bow-like loops (TBL) and the region I (short loops region) of the Z lampbrush chromosome. These clones, pCZTH12-8 particularly notably, hybridized also to the TBLs of lampbrush bivalents 1–4 of chicken. Both sequence are transcribed in the lampbrush stage oocytes on the Z chromosome and on other macrobivalents. The subfragment of pCZTH5-8 which hybridizes to the TBLs and the insert of pCZTH12-8 contain regions that are closely similar in sequence. The pCZTH5-8 sequence has no internal repeats and may be part of the 24-kb macrosatellite repeating unit that is evident afterNhel digestion of the genomic DNA. A cloned 24-kb unit, pFN-1, does not show significant DNA curvature, but cytosines of its CpG dinucleotides may be highly methylatedin vivo. This contrasts with the repeat sequences of the W heterochromatin which not only have highly methylated CpG but are also strongly curved. The 24-kb unit is repeated about 830 times in the diploid genome of a female chicken, suggesting that nearly the entire terminal heterochromatin on the Z chromosome consists of this macrosatellite family. Sequences of the greater part of the pCZTH5-8 are restricted to the genusGallus but the sequence of one subregion which hybridizes to TBLs is present in the genomes of the order Galliformes.accepted for publication by M. Schmid     

Preservation of pancreas in the University of Wisconsin solution supplemented with AP39 reduces reactive oxygen species production and improves islet graft function

Ischemia-reperfusion injury (IRI) results in increased rates of delayed graft function and early graft loss. It has recently been reported that hydrogen sulfide (H₂S) protects organ grafts against prolonged IRI. Here, we investigated whether the preservation of pancreas in University of Wisconsin (UW) solution supplemented with AP39, which is a mitochondrial-targeted H₂S donor, protected pancreatic islets against IRI and improved islet function. Porcine pancreata were preserved in the UW solution with AP39 (UW + AP39) or the vehicle (UW) for 18 h, followed by islet isolation. The islet yields before and after purification were significantly higher in the UW + AP39 group than in the UW group. The islets isolated from the pancreas preserved in UW + AP39 exhibited significantly decreased levels of reactive oxygen species (ROS) production and a significantly increased mitochondrial membrane potential as compared to the islets isolated from the pancreas preserved in the vehicle. We found that the pancreas preserved in UW + AP39 improved the outcome of islet transplantation in streptozotocin-induced diabetic mice. These results suggest that the preservation of pancreas in UW + AP39 protects the islet grafts against IRI and could thus serve as a novel clinical strategy for improving islet transplantation outcomes.     

Impact of the COVID-19 pandemic on pathological autopsy practices in Japan

During the coronavirus disease 2019 (COVID-19) pandemic, autopsies have provided valuable insights into the pathogenesis of COVID-19. The precise effect of this pandemic on autopsy procedures in Japan, especially in instances unrelated to COVID-19, has not yet been established. Therefore, we conducted a questionnaire survey from December 2020 to January 2021 regarding the status of pathological autopsy practices in Japan during the first year of the COVID-19 pandemic. The questionnaire was sent to 678 medical facilities with pathologists, of which 227 responded. In cases where a confirmed diagnosis of COVID-19 was not made at the time of autopsy, many facilities counted them as suspected COVID-19 cases if pneumonia was suspected clinically. At around half of the sites, autopsies were prohibited for suspected COVID-19 cases. In addition, the number of autopsies of non-COVID-19 cases during the pandemic period was also investigated, and a significant decrease was observed compared with the incidence in the pre-pandemic period. The COVID-19 pandemic has affected not only the autopsies of COVID-19 cases but also the entire practice of pathological autopsies. It is necessary to establish a system that supports the implementation of pathological autopsy practices during the pandemic of an emerging infectious disease.     

Long thoracic nerve paralysis associated with thoracic outlet syndrome

Two cases of long thoracic nerve palsy associated with thoracic outlet syndrome are reported. Both patients had abnormal posture, with low-set shoulders and winged scapulae. Clinically there was weakness of the serratus anterior muscle with partial denervotion on electromyography. The diagnosis of thoracic outlet syndrome was based on positive vascular tests and brachial plexus nerve compression symptoms induced by the vascular testing positions. An orthosis that held the shoulder in an elevated position was used in both cases. Complete recovery of shoulder function and relief of the symptoms was achieved in both cases at 8 and 13 months, respectively, after application of the orthosis.     

Efficacy of an echo contrast agent, SH/TA-508, in color doppler sonography of mass lesions in urology

We performed a clinical phase III study with a galactosebased ecoo contrast agent, SH/TA-508, to evaluate its efficacy, safety, and usefulness for mass lesions in urology. SH/TA-508 was prepared as a suspension containing stabilized micro-air bubbles by adding water for injection just before use. SH/TA-508 was administered into the antecubital vein at an initial dose of 300 mg/ml × 5 ml followed by higher doses of 400 mg/ml × 4 ml, 300 mg/ ml × 10 ml or 400 mg/ml × 8 ml when a sufficient effect was not obtained. Efficacy was evaluated by color Doppler signal enhancement, the duration of blood flow signal enhancement, and improvement of diagnostic capacity. Fifty-nine patients with mass lesions in the kidney, prostate, testis, adrenal gland, and bladder were enrolled in the study. Up to the third dose the cumulative efficacy rates (≥2+) of color Doppler signal enhancement and duration of blood flow signal enhancement were 92% and 87%, respectively. Consequently, diagnostic capacity in 76% of the patients was remarkably improved. A light transient angialgia occurred in one patient but no other clinically significant changes were observed. It was confirmed that SH/TA-508 is a safe echo contrast agent that offers satisfactory color Doppler signal enhancement in the urologic organs mentioned above.     

The ulinastatin-induced effect on neuromuscular block caused by vecuronium

We examined the effect of ulinastatin, a protease inhibitor purified from human urine, on neuromuscular block caused by vecuronium. Sixty adult patients were randomly divided into four groups of 15 patients each: ulinastatin-posttetanic count (U-PTC), ulinastatin-train-of-four (U-TOF), control-posttetanic count (C-PTC) or control-train-of-four (C-TOF) group. In the U-PTC and U-TOF groups, a bolus dose of ulinastatin 5000 U/kg was administered 2 min before the injection of vecuronium 0.1 mg/kg. In the C-PTC and C-TOF groups, normal saline was administered instead of ulinastatin. The onset of neuromuscular block in the U-PTC and U-TOF groups was significantly slower than in the C-PTC and C-TOF groups (250+/-49 vs 214+/-35 s, mean +/- SD, P < 0.05). The time from the vecuronium injection to the return of PTC in the U-PTC group was significantly shorter than in the C-PTC group (11.0+/-2.8 vs 17.6+/-6.8 min, P < 0.05). Similarly, times to the returns of T1, T2, T3, and T4 (first, second, third, and fourth stimulation of TOF) in the U-TOF group were significantly shorter than in the C-TOF group (18.5+/-5.0 vs 28.0+/-9.1 min for T1, P < 0.05). PTC in the U-PTC group was significantly higher than in the C-PTC Group 10-30 min after the administration of vecuronium (P < 0.05). T1/control twitch height and TOF ratios in the U-TOF group were significantly higher than those in the C-TOF Group 30-70 min and 40-70 min after the administration of vecuronium, respectively (P < 0.05). Ulinastatin delays the onset of neuromuscular block and hastens its recovery caused by vecuronium. IMPLICATIONS: Ulinastatin delays the onset of neuromuscular block and hastens its recovery caused by vecuronium. This is because ulinastatin may release acetylcholine at the neuromuscular junction and increase hepatic and/or renal clearance of vecuronium.