Functional thrombomodulin expression on epithelial skin tumours as a differentiation marker for suprabasal keratinocytes

Summary In normal human skin, immtmoreactive thrombomodulin (TM) is expressed in a strict differentiation related pattern. solely in suprabasal spinous layer keratinocytes. To evaluate the polential application of TM as a differentiation marker for keratinocyte-derived skin tumours, we have studied immunohistopathological, biochemical and functional TM activities in various skin tumours. Immunoreactive, full sized and enzymatically active TM was expressed in keratinocyte-derived skin tumours (squamous cell carcinoma, seborrhoeic keratosis and partly Bowen's disease), as well as normal epidermal keratinoeytes and endothelial cells. However, no TM was detected in basal cell carcinotnas, senile keratosis or non-squanious epithelial tumours such as malignant melanoma, naevus pigmentosus and Paget's disease. Interestingly, decreased expression was observed in verruca vulgaris. These findings suggested that differentiation-dependent TM expression was restricted to epithelial skin tumours and undetectable on neural crest derived tumours. TM is a differentiation marker for spinous layer keratinocytes and is a useful tool in histopathological study of epithelial tumours.     

Effect of relaxation training on cardiac parasympathetic tone

To examine the hypothesis that the relaxation response is associated with an increase in cardiac parasympathetic tone, the frequency components of heart rate variability during relaxation training were investigated in 16 college students. Electrocardiograms and pneumograms were recorded during a 5-min baseline period followed by three successive 5-min sessions of the autogenic training (relaxation) or by the same periods of quiet rest (control), while subjects breathed synchronously with a visual pacemaker (0.25 Hz). Although neither the magnitude nor the frequeney of respiration showed a significant difference between relaxation and control, the amplitude of the high-frequency component of heart rate variability increased only during relaxation (p= .008). There was no significant difference in the ratio of the low-frequency (0.04–0.15 Hz) to the high-frequency amplitudes. The increased high-frequency amplitude without changes in the respiratory parameters indicates enhanced cardiac parasympathetic tone. Thus, our results support the initial hypothesis of this study. Enhanced cardiac parasympathetic tone may explain an important mechanism underlying the beneficial effect of the relaxation response.     

Diagnosis of Small Pancreatic Carcinoma

A retrospective analysis was performed to evaluate the clinicalsymptoms and abnormal test findings in small pancreatic carcinoma.Five hundred and thirty-six cases of pancreatic carcinoma withthe histology of duct cell carcinoma were collected from 14medical centers in Japan. In 440 of the cases, tumor size wasmeasured at the time of laparotomy or from the resected specimen.Three hundred and seventy-seven patients (86%) had a carcinomalarger than 3.0 cm; only 30% of these were resectable. Sixty-threepatients (14%) had a carcinoma of 3.0 cm or less, with resectabilityof 97%. Detecting a tumor of "3 cm or less" with a high probabilityof resectability is the objective of early diagnosis with theresulting possibility of a cure. In most cases these small carcinomaswere found easily when obstructive jaundice was present (73%).However, the estimated occurrence of obstructive jaundice associatedwith carcinomas of 3 cm or less was only 10% among the totalcases of pancreatic carcinoma studied. Therefore, it is necessaryfor early diagnosis to detect carcinomas of 3 cm or less presentingwithout jaundice. The symptoms of small carcinoma without jaundiceare weight loss, anorexia, upper abdominal pain, back pain anda palpable abdominal mass. Among the various available examinations,endoscopic retrograde cholangiopancreatography, computerizedtomography and ultrasonography were valuable in diagnosing thesesmall carcinomas.     

Relationship between Pathological Characteristics and Radiological Findings on Perfusion MR Imaging of Meningioma

Few studies have reviewed the roles of perfusion magnetic resonance (MR) imaging in the histopathological examination of meningiomas. We analyzed the relationships between radiological findings on perfusion MR imaging and pathological characteristics such as origin of the tumor, mitotic activity, pathological subtype, and perifocal edema formation. The subjects were 21 surgical cases of meningioma preoperatively evaluated by perfusion MR imaging. A region of interest (ROI) was set inside of the tumor, and perifocal edema of the same size, cerebral blood volume (CBV), and cerebral blood flow (CBF) on perfusion MR and diffusion-weighted (DW) imaging were analyzed. These radiological data were evaluated in comparison with histopathological characteristics. On perfusion MR imaging, the average ratio of CBV against the contralateral side was 6.43 (1.13–20.0) and that of CBF was 7.73 (1.34–11.3). There was no significant relationship with perfusion MR imaging data, tumor volume, or perifocal edema volume. However, the large peritumoral edema group often had a higher CBV and CBF than the non-large peritumoral edema group. The skull base group had a significantly higher CBV and lower signal intensity on DW images than the non-skull base group. Signal intensity on DW images was higher in grade II or III than in grade I. Perfusion MR imaging data revealed that the higher ratio of peritumoral edema against tumor size was associated with higher blood flow and blood volume under intratumoral circulatory conditions, and that skull base meningioma had a higher blood volume than non-skull base meningioma.     

EFFECTS OF DIFFERENT DOSES OF THIOPENTONE ON THE INCREASE IN SERUM MYOGLOBIN INDUCED BY SUXAMETHONIUM IN CHILDREN

We have studied the effects of different doses of thiopentoneon the increase in serum myoglobin after administration of suxamethoniumduring inhalation induction of anaesthesia in children. Forty-threechildren were anaesthetized with halothane and nitrous oxidein oxygen and allocated to four groups. group S received suxamethonium1 mg kg^–1 to facilitate intubation; group ST2 receivedthiopentone 2 mg kg^–1 and group ST4 received thiopentone4 mg kg^–1 before administration of suxamethonium 1 mgkg^–1; group N did not receive thiopentone or suxamethonium.Serum myoglobin and creatine kinase (CK) concentrations weremeasured until 60 min after the injection of suxamethonium.Both myoglobin and CK concentrations increased in the threegroups receiving suxamethonium. There were no significant differencesbetween groups S and ST2, but the myo globin concentration wasless in group ST4 than in groups S and ST2. A significant differencein CK concentration was found only between groups ST2 and ST4at 60min. In group N, both values remained reasonably constant.Thiopentone 4mg kg^–1, but not 2 mg kg^–1, attenuatedthe increase. The results indicate that to prevent a markedelevation in serum myoglobin after administration of suxamethonium,thiopentone 4 mg kg^–1 should be administered. Presented in part at the Annual Meeting of the American Societyof Anesthesiology, October 1989 (Anesthesiology 1989; 71: A1046).     

Effects of Gadolinium Chloride on the Rat Lung Following Intratracheal Instillation

The metabolic behavior, clearance, and pulmonary effects ofgadolinium (Gd), one of the rare earth elements, were investigatedafter single intratracheal instillation of gadolinium chloride(GdCl₃) in male Wistar rats. There was a dose-related increasein Gd content of lung tissue. Gd content in the supernatantof bronchoalveolar lavage fluid (BALF) did not exceed 5 µgGd/ BALF even at a dose of 100 µg Gd/rat. Gd in the lungtissue decreased very slowly with a biological half-life of136 days at a dose of 50 µg Gd/rat. On the other hand,Gd content in the super natant of BALF was not detectable after31 days. These results suggest that intratracheally instilledGd can be retained in epithelial lining fluid only to a limitedextent as soluble forms and is deposited in the lung tissueprobably in insoluble forms which are metabolized very slowly.Calcium (Ca) content in BALF increased more rapidly than othertoxicological indices such as lactate dehydrogenase activity,protein concentration, and inflammatory cell counts. In thelung tissue, levels of Ca in Gd-instilled groups did not differfrom the control value. Although these data suggest that theorigin of Ca may be blood plasma, biological and/or toxicologicalsignificance of increased Ca is not known. The number of neutrophilsreached the maximum at 12 hr after instillation, indicatingthat Gd has the potency to cause acute lung toxicity. Summarizingthe observation, Gd instilled intratracheally into rats wasdeposited in the lung tissue in nonsoluble forms with an extremelylong half-life, while the metal caused a rapid and selectiveinfiltration of serum Ca before acute lung toxicity.     

Marked Reduction of Cerebral Vasospasm with Intrathecal Urokinase Infusion Therapy after Endovascular Coil Embolization of the Aneurysmal Subarachnoid Hemorrhage: A Case Series

Delayed cerebral vasospasms after subarachnoid hemorrhage (SAH) are a risk factor for poor prognosis after successful treatment of ruptured intracranial aneurysms. Different strategies to remove clots from the subarachnoid space and prevent vasospasms have different outcomes. Intrathecal urokinase infusion therapy combined with endovascular treatment (EVT) can reduce the incidence of symptomatic vasospasms. To analyze the relationship between symptomatic vasospasms and residual SAHs after urokinase infusion therapy, we retrospectively reviewed the records of 348 consecutive patients managed with EVT and intrathecal urokinase infusion therapy for aneurysmal SAH at our institution between 2010 and 2021. Among them, 163 patients met the study criteria and were classified into two groups according to the presence of residual SAH in the cisterns, Sylvian fissures, and frontal interhemispheric fissure. The incidence of symptomatic vasospasms and the clinical outcomes were assessed. In total, eight (5.0%) patients developed symptomatic vasospasms. Patients with symptomatic vasospasms had a significantly higher incidence of residual SAH in the Sylvian or frontal interhemispheric fissures than those without (P <.0001). No patient with SAHs resolved by urokinase infusion therapy developed symptomatic vasospasms. However, the two groups did not differ significantly in terms of modified Rankin scale scores at discharge. Treatment with intrathecal urokinase infusion after EVT for aneurysmal SAH can substantially reduce the risk of clinically evident vasospasms.     

Regulatory mechanisms of C4b‐binding protein (C4BP)α and β expression in rat hepatocytes by lipopolysaccharide and interleukin‐6

Summary. Background: C4b‐binding protein (C4BP), a multimeric protein structurally composed of α chains (C4BPα) and a β chain (C4BPβ), regulates the anticoagulant activity of protein S (PS). Patients with sepsis have increased levels of plasma C4BP, which appears to be induced by interleukin (IL)‐6. However, it is not fully understood how lipopolysaccharide (LPS) and IL‐6 affect the plasma C4BP antigen level and C4BPα and C4BPβ expression in hepatocytes. Objectives: To assess the effect of LPS and IL‐6 on plasma C4BP, PS–C4BP complex levels, PS activity, and C4BP expression by rat liver in vivo and on C4BP expression by isolated rat hepatocytes in vitro. Results: Plasma C4BP antigen level transiently decreased from 2 to 12 h after LPS (2 mg kg^?1) injection, and then it abruptly increased up to 24 h after LPS injection. Plasma C4BP antigen level increased until 8 h after IL‐6 (10 μg kg^?1) injection, and then gradually decreased up to 24 h after IL‐6 injection. LPS significantly decreased the protein and mRNA expression of both C4BPα and C4BPβ in rat hepatocytes, and this effect was inhibited by NFκB and MEK/ERK inhibitors. IL‐6 mediated increase in C4BPβ expression in rat hepatocytes, which leads to increased plasma PS–C4BP complex level and to decreased plasma PS activity, was inhibited by inhibition of STAT‐3. Conclusion: LPS decreases both C4BPα and C4BPβ expression via the NFκB and MEK/ERK pathways, whereas IL‐6 specifically increases C4BPβ expression via the STAT‐3 pathway, causing an increase in plasma PS–C4BP complex, and thus decreasing the anticoagulant activity of PS.