Distribution of α2-macroglobulin in normal,inflammatory, and tumor tissues in rats

Distribution of uptake and catabolism of intravenously administered¹²⁵l-labeled rat ₂-macroglobulin(¹²⁵I-₂MG) were examined in normal, inflammatory, and tumor tissues of rats. Clearance of intravenously administered [¹²⁵l]₂MG from the circulation was rapid. Accumulation of this compound into inflammatory tissue was 2–3 times more extensive than in normal tissues. The accumulation into sarcoma tissue was much less. Radioactivity in TCA-PTA precipitates remained fairly constant for the first 12 h in inflammatory tissue and for the first 24 h in sarcoma. These patterns of accumulation were never observed in the normal tissues. As the kidney preferentially accumulated large amounts of [¹²⁵l]₂MG in the nondegraded form and its degradation products, the tissue may play a special role in the metabolism of ₂MG. Rapid clearance from the circulation and relatively small amounts of accumulation in tissues suggest that ₂MG may function as a protease inhibitor, mainly in the circulation rather than in the tissues.     

Cervical myelopathy due to OPLL: clinical evaluation by MRI and intraoperative spinal sonography

BACKGROUND: Concerning the relationship between morphology and clinical outcome, there have been many reports using computed tomography/myelography but not so many using axial magnetic resonance imaging (MRI) of the spinal cord. This is the first report to correlate axial cord image, intensity changes in MRI, and cord expansion pattern using intraoperative ultrasonography. OBJECTIVE: The objectives were to correlate MRI studies, axial cord images/expansion, and changes in MRI intensity to see if there is a direct prognostic significance to these changes and to determine whether preoperative axial MRI images of the spinal cord predict recovery from compressive myelopathy. METHODS: Posterior cervical decompressions with laminoplasty were performed in 44 patients with cervical myelopathy due to ossification of the posterior longitudinal ligament. On T2-weighted MR images, the cross-sectional shape of the cord at the level of maximal compression was categorized as boomerang, teardrop, or triangle. Additionally, with use of intraoperative ultrasonography, the expansion pattern of the cord that occurred intraoperatively was contrasted with that seen on postoperative MR images. RESULTS: Clinical recovery rates were the worst for those with triangular, intermediate for those with boomerang, and the best for those with teardrop shape. Preoperative low T1 and high T2 signals were found in most cases with triangular cord configurations. Triangular cord configurations showed the least expansion among the three categorized spinal cords. CONCLUSION: Patients with triangular deformity of the cord have atrophy as confirmed on MR studies where there is a low T1 and high T2 signal in the cord. Poor postoperative clinical recovery correlates with the lack of postoperative cord expansion on either MR or ultrasound evaluations. Those with either teardrop or boomerang deformities demonstrate a relatively good recovery rate.     

Prevalence of Synchronous Colorectal Neoplasms Detected by Colonoscopy in Patients with Gastric Cancer

Purpose Our purpose was to study the characteristics of colorectal neoplasms in patients with gastric cancer (GC). Methods The study group comprised GC patients who underwent colonoscopy before resection of their GC. We examined the prevalence, site, and histology of colorectal neoplasms, as well as the clinicopathological features and treatment of the patients who had synchronous colorectal cancers (CRC). The logistic regression model was applied to investigate the features of the GC patients with concurrent CRC. Results We studied 466 GC patients (mean age 64.5 years; 147 women, 319 men), 143 (31%) of whom had a family history of gastrointestinal cancer. Synchronous colorectal adenoma and cancer were detected in 182 (39%) and 18 (4%) patients, respectively. Among the 18 synchronous CRCs, 11 were in the early stages and 10 of these were resected endoscopically. The other eight required simultaneous open radical surgery. All the GC patients with synchronous CRC were older than 50 years. Statistical analysis did not show a significant difference between the features of the patients with and those without concurrent CRC. Conclusions The possibility of synchronous colorectal neoplasms in GC patients cannot be disregarded in clinical practice; however, screening of the large bowel may not be necessary in GC patients younger than 50 years.     

Effect of three flavonoids isolated from Japanese Polygonum species on superoxide generation in human neutrophils

Three flavonoids, quercetin 3- O-glucoside-2'-gallate (QGG), quercetin 3- O-rhamnoside-2'-gallate (QRG) and kaempferol 3- O-glucoside-2'-gallate (KGG) were isolated from Japanese Polygonum species. The effect of these flavonoids on stimulus-induced superoxide generation in human neutrophils was assayed by measuring the reduction of cytochrome c. The tyrosyl or serine/threonine phosphorylation of neutrophil proteins and the translocation of p4(phox) and p67(phox) to the cell membrane were detected using specific monoclonal antibodies. The flavonoids used in this experiment significantly suppressed stimulus-induced superoxide generation in a concentration-dependent manner. FMLP-induced tyrosyl phosphorylation or PMA-induced serine/threonine phosphorylation and the translocation of the cytosolic proteins p47(phox) and p67(phox) to the cell membrane were suppressed in parallel to the suppression of the stimulus-induced superoxide generation.     

Normal motor learning during pharmacological prevention of Purkinje cell long-term depression

Systemic delivery of (1R-1-benzo thiophen-5-yl-2[2-diethylamino)-ethoxy] ethanol hydrochloride (T-588) prevented long-term depression (LTD) of the parallel fiber (PF)-Purkinje cell (PC) synapse induced by conjunctive climbing fiber and PF stimulation in vivo. However, similar concentrations of T-588 in the brains of behaving mice and rats affected neither motor learning in the rotorod test nor the learning of motor timing during classical conditioning of the eyeblink reflex. Rats given doses of T-588 that prevented PF-PC LTD were as proficient as controls in learning to adapt the timing of their conditioned eyeblink response to a 150- or 350-ms change in the timing of the paradigm. The experiment indicates that PF-PC LTD under control of the climbing fibers is not required for general motor adaptation or the learning of response timing in two common models of motor learning for which the cerebellum has been implicated. Alternative mechanisms for motor timing and possible functions for LTD in protection from excitotoxicity are discussed.     

Casual C peptide index: Predicting the subsequent need for insulin therapy in outpatients with type 2 diabetes under primary care

BackgroundEvaluation of residual beta cell function is indispensable in patients with type 2 diabetes as it informs not only diagnoses but also appropriate treatment modalities. However, there is a lack of convenient biomarkers for residual beta cell function. Therefore, we evaluated endogenous insulin level as a biomarker in outpatients who were being treated with insulin therapy and in patients who were introduced to insulin therapy after 4 years.MethodsData of 174 outpatients with type 2 diabetes (50% male) whose glycemia was moderately controlled (glycated A1c 7.3% [5.2%–14.8%]) were reviewed. Twenty patients whose estimated glomerular filtration rate was lower than 30 ml/min/1.73 m² were excluded from the evaluation of endogenous insulin level with both casual C‐peptide index (C‐CPI) and urinary C‐peptide/creatinine ratio (determined at any time, generally 1–2 h after breakfast). Patients were stratified based on the provision of insulin therapy.ResultsC‐CPI and UCPCR were significantly lower in the insulin‐treated patients than in the insulin‐untreated patients (0.9 vs. 2.2, p < 0.0001; 24.7 vs. 75.5, p = 0.0003, respectively). Moreover, C‐CPI were significantly lower in the insulin‐requiring patients for 4 years than in the insulin‐unrequiring patients (1.0 vs. 1.7, p = 0.0184). The multivariate logistic regression analysis revealed that both indicators of insulin secretion influenced the requirement for insulin therapy, but C‐CPI could serve as the most convenient and useful biomarker for not only current insulin therapy requirements (p = 0.0002) but also the subsequent requirement for insulin therapy (p = 0.0008).ConclusionsC‐CPI could be determined easily, and it was found to be a more practical marker for outpatients; therefore, our findings would have critical implications for primary care.