ABSTRACT
BACKGROUND AND PURPOSE: Conduction block is a pathognomonic feature of immune-mediated neuropathies. The aim of this study was to advance understanding of pathophysiology and conduction block in chronic inflammatory demyelinating polyneuropathy (CIDP) and multifocal motor neuropathy (MMN). METHODS: A multimodal approach was used, incorporating clinical phenotyping, neurophysiology, immunohistochemistry and structural assessments. RESULTS: Of 49 CIDP and 14 MMN patients, 25% and 79% had median nerve forearm block, respectively. Clinical scores were similar in CIDP patients with and without block. CIDP patients with median nerve block demonstrated markedly elevated thresholds and greater threshold changes in threshold electrotonus, whilst those without did not differ from healthy controls in electrotonus parameters. In contrast, MMN patients exhibited marked increases in superexcitability. Nerve size was similar in both CIDP groups at the site of axonal excitability. However, CIDP patients with block demonstrated more frequent paranodal serum binding to teased rat nerve fibres. In keeping with these findings, mathematical modelling of nerve excitability recordings in CIDP patients with block support the role of paranodal dysfunction and enhanced leakage of current between the node and internode. In contrast, changes in MMN probably resulted from a reduction in ion channel density along axons. CONCLUSIONS: The underlying pathologies in CIDP and MMN are distinct. Conduction block in CIDP is associated with paranodal dysfunction which may be antibody-mediated in a subset of patients. In contrast, MMN is characterized by channel dysfunction downstream from the site of block.
Subject(s)
Neural Conduction/physiology , Peripheral Nerves/physiopathology , Polyneuropathies/physiopathology , Polyradiculoneuropathy, Chronic Inflammatory Demyelinating/physiopathology , Adult , Animals , Axons/physiology , Female , Humans , Male , Middle Aged , RatsABSTRACT
OBJECTIVE: The utility of quantitative muscle ultrasound as a marker of disease severity in Charcot-Marie-Tooth (CMT) disease subtypes was investigated. METHODS: Muscle ultrasound was prospectively performed on 252 individual muscles from 21 CMT patients (9 CMT1A, 8 CMTX1, 4 CMT2A) and compared to 120 muscles from 10 age and gender-matched controls. Muscle ultrasound recorded echogenicity and thickness in representative muscles including first dorsal interosseus (FDI) and tibialis anterior (TA). RESULTS: Muscle volume of FDI and thickness of TA correlated with MRC strength. Muscle echogenicity was significantly increased in FDI (65.05 vs 47.09; p<0.0001) and TA (89.45 vs 66.30; p<0.0001) of CMT patients. In TA, there was significantly higher muscle thickness (23 vs 18 vs 16mm; p<0.0001) and lower muscle echogenicity (80 vs 95 vs 108; p<0.0001) in CMT1A compared to CMTX1 and CMT2A. This corresponded to disease severity based on muscle strength (MRC grading CMT1A vs CMTX1 vs CMT2A: 59 vs 48 vs 44; p=0.002). CONCLUSION: In CMT, quantitative muscle ultrasound of FDI and TA is a useful marker of disease severity. SIGNIFICANCE: The current findings suggest that quantitative muscle ultrasound has potential as a surrogate marker of disease progression in future interventional trials in CMT.
Subject(s)
Charcot-Marie-Tooth Disease/diagnostic imaging , Muscle, Skeletal/diagnostic imaging , Ultrasonography/methods , Adult , Charcot-Marie-Tooth Disease/physiopathology , Female , Humans , Male , Middle Aged , Muscle, Skeletal/physiopathology , Neural Conduction/physiology , Prospective StudiesABSTRACT
While the past 2 decades have witnessed an increasing understanding of amyotrophic lateral sclerosis (ALS) arising from East Asia, particularly Japan, South Korea, Taiwan and China, knowledge of ALS throughout the whole of Asia remains limited. Asia represents >50% of the world population, making it host to the largest patient cohort of ALS. Furthermore, Asia represents a diverse population in terms of ethnic, social and cultural backgrounds. In this review, an overview is presented that covers what is currently known of ALS in Asia from basic epidemiology and genetic influences, through to disease characteristics including atypical phenotypes which manifest a predilection for Asians. With the recent establishment of the Pan-Asian Consortium for Treatment and Research in ALS to facilitate collaborations between clinicians and researchers across the region, it is anticipated that Asia and the Pacific will contribute to unravelling the uncertainties in ALS.
Subject(s)
Amyotrophic Lateral Sclerosis/complications , Amyotrophic Lateral Sclerosis/epidemiology , Motor Neuron Disease/complications , Motor Neuron Disease/epidemiology , Amyotrophic Lateral Sclerosis/genetics , Amyotrophic Lateral Sclerosis/mortality , Asia/epidemiology , Disease Progression , Humans , Motor Neuron Disease/genetics , Motor Neuron Disease/mortality , Phenotype , SyndromeABSTRACT
BACKGROUND: A severe earthquake occurred in Japan on 11 March 2011. The giant tsunami devastated many coastal communities in eastern Japan and caused the Fukushima Dai-ichi nuclear power plant incident. The Japanese government conducted a large-scale survey of residents affected by the nuclear and natural disasters in Fukushima prefecture and in response to the government's request, H University dispatched a Radiation Exposure Research Team to Fukushima. PURPOSE: This article explains the activities of the Radiation Exposure Research Team and the role of nurses in a nuclear disaster. CONCLUSION: As a nurse in the field of radiation medicine, our role is to protect the health of those affected and to reduce their anxiety. In addition, as the persons responsible for implementing these projects, it is also necessary that we educate and foster the development of medical care personnel with the appropriate knowledge and skills to carry out the measures required.
Subject(s)
Disasters , Earthquakes , Fukushima Nuclear Accident , Nuclear Power Plants , Nurse's Role , Radiation Injuries/nursing , Tsunamis , Emergency Nursing/organization & administration , Humans , Japan , Radioactive Hazard ReleaseABSTRACT
OBJECTIVES: To study the utility of muscle ultrasound (US) for detection of fasciculations and its contribution to diagnosis in amyotrophic lateral sclerosis (ALS). Fasciculations are characteristic features of ALS, and US can detect them easily and reliably. New diagnostic criteria for ALS, the Awaji algorithm, reintroduced fasciculations as evidence of acute denervation equivalent to that of fibrillations and positive sharp waves. METHODS: In 81 consecutive patients with sporadic ALS, we prospectively performed needle EMG and US in 6 muscles (tongue, biceps brachii, first dorsalis interosseous, paraspinalis, vastus lateralis, and tibialis anterior), and diagnostic category were determined by revised El Escorial criteria and Awaji criteria. RESULTS: Fasciculations were much more frequently detected by US than by EMG in the tongue (60% vs 0%), biceps brachii (88% vs 60%), and tibialis anterior muscles (83% vs 45%). The proportion of the patients with definite or probable ALS was 48% by revised El Escorial criteria and 79% by Awaji criteria using US. CONCLUSIONS: Muscle US is a practical and efficient tool to detect fasciculations, particularly in the tongue. A combination of US and EMG substantially increases the diagnostic sensitivity of ALS.
Subject(s)
Amyotrophic Lateral Sclerosis/diagnostic imaging , Amyotrophic Lateral Sclerosis/physiopathology , Fasciculation/diagnostic imaging , Fasciculation/physiopathology , Ultrasonography, Doppler/methods , Adult , Aged , Aged, 80 and over , Algorithms , Electromyography , Female , Humans , Male , Middle Aged , Muscle, Skeletal/diagnostic imaging , Muscle, Skeletal/physiopathology , Sensitivity and SpecificityABSTRACT
POEMS (polyneuropathy, organomegaly, endocrinopathy, M-protein and skin changes) syndrome is a rare cause of demyelinating neuropathy with monoclonal plasma cell proliferation, and POEMS neuropathy is usually chronically progressive. Herein, the authors report a 34-year-old woman with POEMS syndrome presenting as acute polyneuropathy. Within 2 weeks of disease onset, she became unable to walk with electrodiagnostic features of demyelination and was initially diagnosed as having Guillan-Barré syndrome. Other systemic features (oedema and skin changes) developed later, and an elevated serum level of vascular endothelial growth factor led to the diagnosis of POEMS syndrome. She received high-dose chemotherapy with autologous peripheral blood stem cell transplantation, resulting in good recovery. The authors also reviewed patterns and speed of progression of neuropathy in the 30 patients with POEMS syndrome; 22 (73%) of them were unable to walk independently with the median period of 9.5 months from POEMS onset (range 0.5-51 months). Whereas the speed of neuropathy progression varies considerably among patients, some POEMS patients can show acute or subacute polyneuropathy. The early diagnosis and treatment could result in rapid improvement as shown in the present patient.
Subject(s)
Disease Progression , Guillain-Barre Syndrome/diagnosis , POEMS Syndrome/diagnosis , Adult , Aged , Female , Humans , Male , Middle Aged , POEMS Syndrome/blood , Vascular Endothelial Growth Factor A/bloodABSTRACT
BACKGROUND: Previous studies have shown that anti-GQ1b antibodies induce massive neuromuscular blocking. If anti-GM1 and -GD1a antibodies have similar effects on the neuromuscular junction (NMJ) in human limb muscles, this may explain selective motor involvement in axonal Guillain--Barré syndrome (GBS). METHODS: Axonal-stimulating single-fibre electromyography was performed in the extensor digitorum communis muscle of 23 patients with GBS, including 13 with the axonal form whose sera had a high titre of serum IgG anti-GM1 or -GD1a antibodies. RESULTS: All patients with axonal or demyelinating GBS showed normal or near-normal jitter, and no blocking. CONCLUSION: In both axonal and demyelinating GBS, neuromuscular transmission is not impaired. Our results failed to support the hypothesis that anti-GM1 or -GD1a antibody affects the NMJ. In GBS, impulse transmission is presumably impaired in the motor nerve terminal axons proximal to the NMJ.
Subject(s)
Axons/physiology , Guillain-Barre Syndrome/physiopathology , Neuromuscular Junction/physiopathology , Synaptic Transmission/physiology , Adult , Aged , Autoantibodies/blood , Electromyography , Female , G(M1) Ganglioside/analogs & derivatives , G(M1) Ganglioside/immunology , Guillain-Barre Syndrome/diagnosis , Humans , Immunoglobulin G/blood , Male , Middle Aged , Muscle, Skeletal/innervation , Young AdultABSTRACT
BACKGROUND: A multicenter prospective clinical trial was carried out in 9 National Hospitals in Japan to elucidate the time-dependent change in urinary Type IV collagen excretion rate of Type II diabetes mellitus (DM) patients, and to investigate whether an angiotensin-converting enzyme inhibitor (ACE-I) or probucol is effective in preventing progression of renal involvement of diabetics by evaluating urinary Type IV collagen excretion. METHODS: Normo- and microalbuminuric patients with Type II DM were recruited. Patients were assigned to either the control (n = 88), ACE-I (n = 43) or probucol (n = 37) group and treated for 24 months. Besides albumin excretion rate (AER), urinary Type IV collagen excretion rate was also measured. RESULTS: Although, AER, urinary N-acetyl-beta-D-glucosaminidase and beta2-microglobulin excretion rates in the control group did not vary over 24 months, urinary Type IV collagen excretion rate in the control group increased time-dependently (p < 0.01 vs baseline at 18 months and p < 0.005 vs baseline at 24 months). In the ACE-I and probucol groups, time-dependent increases in urinary Type IV collagen excretion rates were not observed. In the ACE-I group, the urinary Type IV collagen excretion rate was significantly lower than that in the control group at 24 months (p < 0.05). In the probucol group, the urinary Type IV collagen excretion rate was significantly lower than that in the control group at 6 months (p < 0.05). In the ACE-I group, AER decreased significantly compared with baseline at 18 months (p < 0.05) and at 24 months (p < 0.005). CONCLUSIONS: ACE-I has a beneficial effect and probucol may have a beneficial effect in preventing the progression of early diabetic nephropathy. Measurement of the urinary Type IV collagen excretion rate in combination with AER would be useful for the management of early renal involvement in Type II DM.
Subject(s)
Albuminuria/drug therapy , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Antioxidants/therapeutic use , Collagen Type IV/urine , Diabetes Mellitus, Type 2/urine , Diabetic Nephropathies/drug therapy , Probucol/therapeutic use , Acetylglucosaminidase/urine , Adult , Aged , Antioxidants/pharmacology , Cholesterol/blood , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/complications , Diabetic Nephropathies/etiology , Diabetic Nephropathies/urine , Female , Glycated Hemoglobin/analysis , Humans , Male , Middle Aged , Probucol/pharmacology , Prospective Studies , Time FactorsABSTRACT
A case of adenoid cystic carcinoma (ACC) of the breast in a 66-year-old woman is reported herein. ACC accounts for about 0.1% of all breast cancers. Our patient presented with a small, elastic and hard mass, measuring 2.0x2.0 cm, between both outer quadrants of the right breast. Although physical examination, ultrasonography and magnetic resonance (MR) mammography suggested a benign tumor, aspiration biopsy cytology (ABC) was performed twice, and the second ABC specimen was evaluated as suspicious for breast carcinoma. Breast conserving surgery with a level II lymph node dissection was subsequently performed. There was no lymph node metastases and estrogen receptor (ER) status was negative. Light microscopy revealed various growth patterns, with the cells showing biphasic cellularity. According to immunohistochemical analyses, CEA, actin and vimentin were positive, S-100 protein was negative, and the cytokeratin reaction was partially positive. Therefore, ACC of the breast was diagnosed. Although ACC of the breast is a rare neoplasm, it should be considered in the differential diagnosis even if various diagnostic imaging studies suggest a benign tumor of the breast. Awareness of this tumor will help prevent misdiagnosis.
Subject(s)
Breast Neoplasms/diagnosis , Carcinoma, Adenoid Cystic/diagnosis , Actins/analysis , Aged , Breast Neoplasms/chemistry , Carcinoembryonic Antigen/analysis , Carcinoma, Adenoid Cystic/chemistry , Diagnostic Imaging/methods , Female , Humans , Japan , Magnetic Resonance Imaging/methods , Mammography , Preoperative Care , S100 Proteins/analysis , Vimentin/analysisABSTRACT
The herniation of small bowel through Winslow's foramen is a rare type of internal hernia which can cause ileus; however, a hernia traversing the lesser sac is even more unusual. To the best of our knowledge, only 25 cases of herniation through Winslow's foramen and 10 cases of lesser sac hernia have been reported in the Japanese literature. We describe herein the case of a 33-year-old man who presented to our hospital complaining of abdominal pain in whom a plain abdominal radiograph revealed small bowel gas with air-fluid levels, suggesting ileus. Following admission, an ileus tube was inserted, but the intestinal shadow did not improve and surgery was performed based on suspicion of an internal hernia. Approximately 100 cm of ileum was found to have herniated through a defect in the lesser omentum after passing through Winslow's foramen. Since the herniated bowel was viable, manual reduction without resection was performed. The patient had a satisfactory postoperative course, and was discharged on postoperative day 11. There are many unknown aspects surrounding the etiology of Winslow's foramen hernia and lesser sac hernia, and although internal hernia is a rare cause of ileus, its possibility should be kept in mind.
Subject(s)
Ileal Diseases/epidemiology , Omentum , Adult , Hernia/diagnostic imaging , Hernia/epidemiology , Herniorrhaphy , Humans , Ileal Diseases/diagnostic imaging , Ileal Diseases/surgery , Male , RadiographyABSTRACT
We report a rare case of hypothermia with acute renal failure in a patient suffering from diabetic nephropathy. A 71-year-old male who had been receiving insulin therapy for the treatment of diabetes mellitus complicated with advanced diabetic nephropathy since 1998 was malnourished with an extremely decreased muscle mass. Without any prolonged exposure to excessively low external temperatures or hypothyroidism, pituitary insufficiency, adrenal insufficiency, sepsis, hypoglycemia, and diabetic ketoacidosis, acute hypothermia appeared together with an aggravation of diabetic nephropathy. His skin temperature fell to below measurable levels and his rectal temperature fell to 30.0 degrees C. His consciousness was drowsy and the hypothermia was not accompanied by shivering. Skeletal muscle is known to play an important role as a center of heat production and shivering thermogenesis in skeletal muscle mainly operates on acute cold stress. Therefore, in this case, hypothermia may have occurred because the shivering thermogenesis could not fully act on the acute cold stress due to the dramatically reduced muscle mass. We should always keep in mind that older, malnourished diabetic patients can easily suffer from impairments of the thermoregulatory system.
Subject(s)
Acute Kidney Injury/complications , Diabetic Nephropathies/complications , Hypothermia/diagnosis , Hypothermia/etiology , Nutrition Disorders/complications , Acute Kidney Injury/blood , Acute Kidney Injury/therapy , Aged , Anti-Bacterial Agents/therapeutic use , Cachexia/etiology , Creatinine/blood , Diabetic Nephropathies/blood , Diabetic Nephropathies/therapy , Glucose/administration & dosage , Humans , Hyperthermia, Induced , Hypothermia/blood , Hypothermia/therapy , Infusions, Intravenous , Male , Oxygen Inhalation Therapy , Renal Dialysis , Urinary Tract Infections/complications , Urinary Tract Infections/diagnosis , Urinary Tract Infections/drug therapyABSTRACT
Studies on human cell hybrids between a cervical carcinoma cell line, HeLa, and normal fibroblasts have indicated that their tumorigenicity is under the control of a putative tumor suppressor on chromosome 11. We have previously demonstrated that a tumorigenic cell hybrid CGL4 expresses a larger glucose transporter, GLUT1, due to altered glycosylation when compared to the nontumorigenic counterpart CGL1. In this study, we demonstrated this glycosylation change in GLUT1 in gamma-ray-induced tumorigenic mutants (GIMs) isolated from CGL1 cells as expressing a tumor-associated surface antigen, intestinal alkaline phosphatase. In contrast, GLUT1 in the gamma-irradiated nontumorigenic control cells (CONs) did not show this alteration. In accordance with this glycosylation change, affinity to 2-deoxyglucose in these GIM clones was increased by about twofold when compared to the nontumorigenic CONs. These results suggest a close correlation between the glycosylation change in GLUT1 with increased affinity to D-glucose and tumorigenicity of these human cell hybrids.
Subject(s)
Cell Transformation, Neoplastic/radiation effects , Monosaccharide Transport Proteins/metabolism , Alkaline Phosphatase/metabolism , Biological Transport , Deoxyglucose/metabolism , Fibroblasts , Gamma Rays , Glucose Transporter Type 1 , Glycosylation/radiation effects , HeLa Cells , Humans , Hybrid Cells , Kinetics , Monosaccharide Transport Proteins/chemistry , Monosaccharide Transport Proteins/radiation effects , Oligosaccharides/chemistry , Oligosaccharides/isolation & purificationABSTRACT
This report describes a 37-year-old man presenting with a gait disturbance due to spastic paraparesis. Physical findings showed typical features of Albright's hereditary osteodystrophy, including short stature, obesity, brachydactyly and dental hypoplasia. He was diagnosed as having pseudohypoparathyroidism type Ia, on the basis of his hypocalcaemia, hyperphosphataemia, increased plasma level of parathyroid hormone (PTH), and the unresponsiveness to exogenous PTH loading of his urinary excretion of both nephrogenous cyclic adenosine monophosphate and phosphate. Magnetic resonance imaging and myelographic computed tomographic scans clearly demonstrated severe compression of the spinal cord at T 9/10 by tumour-like ossifications of the paravertebral ligaments. Neurosurgical decompression therapy was, therefore, performed to alleviate his spastic paraparesis. This was a rare case of pseudohypoparathyroidism complicated with spinal cord compression caused by ectopic ossification of the ligaments.
Subject(s)
Ossification, Heterotopic/complications , Pseudohypoparathyroidism/complications , Spinal Cord Compression/complications , Adult , Calcium/blood , Cyclic AMP/urine , Humans , Magnetic Resonance Imaging , Male , Ossification, Heterotopic/diagnosis , Paraparesis, Tropical Spastic/complications , Parathyroid Hormone/blood , Phosphates/blood , Phosphates/urine , Pseudohypoparathyroidism/diagnosis , Spinal Cord Compression/diagnosis , Tomography, X-Ray ComputedABSTRACT
A 51-year-old male was admitted to our hospital because of diabetic ketoacidosis. His symptoms were promptly improved with intensive insulin therapy, but his plasma glucagon immunoreactivity measured by the OAL-123 radioimmunoassay (RIA) system showed persistently high values (3,090-3,210 pg/ml). A computed tomographic scan, abdominal angiography and endoscopic examination of his gastrointestinal tract showed no evidence of glucagonoma. After removing the immunoglobulin fraction from the plasma, his immunoreactive plasma glucagon level returned to normal. Moreover, the immunoglobulin G fraction purified from the patient's plasma inhibited the binding of [125I]glucagon to rabbit antiglucagon antiserum, OAL-123. Dot-blot analysis demonstrated that the immunoglobulin G of this patient cross-reacted against OAL-123. Therefore, it was considered that the prominent hyperglucagonemia in this patient was due to the presence of IgG, which interfered with the measurement of plasma-immunoreactive glucagon.
Subject(s)
Diabetes Mellitus, Type 1/blood , Glucagon/blood , Immunoglobulin G/blood , Radioimmunoassay , Diabetic Ketoacidosis/blood , Diabetic Ketoacidosis/drug therapy , False Positive Reactions , Humans , Insulin/therapeutic use , Male , Middle AgedABSTRACT
To characterize the mechanisms of insulin resistance in liver cirrhosis (LC), we estimated the peripheral tissue sensitivity and responsiveness to insulin using the euglycemic clamp technique and determined the insulin binding to erythrocytes in patients with compensated LC as well as in patients with non-insulin dependent diabetes mellitus (NIDDM). The insulin dose-response curves of the glucose metabolic clearance rates (MCR) were shifted to the right and downward both in patients with LC and NIDDM, indicating a reduced sensitivity and responsiveness to insulin. In the cirrhotics, MCR at the maximally effective insulin level, an index of insulin responsiveness, was correlated with fasting insulin levels (r = -0.57, P < 0.01) and sigma BG in 75 gOGTT (r = -0.43, P < 0.05), but no correlations were found between them and the diabetics. Although specific insulin bindings to erythrocytes were significantly lower in patients both with LC and NIDDM, Scatchard analysis revealed a significant decrease in the number of insulin receptors in the cirrhotics, and a decrease in the empty-site affinity in the diabetics. These findings suggest that insulin resistance in LC consists of a combination of binding and postbinding defects. The latter defect may be caused by basal hyperinsulinemia and contribute to the development of glucose intolerance. Although binding and postbinding abnormalities are also found in NIDDM, the mechanisms of insulin resistance in LC and NIDDM may be different.
Subject(s)
Diabetes Mellitus, Type 2/physiopathology , Insulin Resistance , Insulin/pharmacokinetics , Liver Cirrhosis/physiopathology , C-Peptide/blood , Dose-Response Relationship, Drug , Erythrocytes/metabolism , Fatty Acids, Nonesterified/blood , Female , Glucagon/blood , Glucose Clamp Technique , Glucose Tolerance Test , Growth Hormone/blood , Humans , Hydrocortisone/blood , Male , Metabolic Clearance Rate , Middle Aged , Receptor, Insulin/metabolismABSTRACT
To elucidate the characteristics of diabetic nodular lesions and the process of progression of diabetic glomerulosclerosis, kidney specimens obtained from 185 patients with non-insulin-dependent diabetes mellitus (NIDDM) were observed using light, electron, and immunofluorescence microscopes. The results suggest the following. First, there are two distinct subtypes of nodular lesions: One is formed by the progression and expansion of diffuse lesions; the other, showing a concentrically layered structure, is probably formed in the process of reconstruction of mesangiolysis. Second, there are three phases in the process of progression of diabetic glomerulosclerosis: In the first phase, arteriolosclerosis and diffuse lesions appear; in the second phase, mesangiolysis and nodular lesions develop in association with moderately advanced arteriolosclerosis; and in the third phase, exudative lesions and hyalinized glomeruli appear in association with advanced arteriolosclerosis together with advanced interstitial lesions. In the progression of the phases and in the development of mesangiolysis and layered nodular lesions, disturbed blood flow into glomeruli in consequence of diabetic arteriolosclerosis could be essential.
Subject(s)
Arteriosclerosis/pathology , Diabetes Mellitus, Type 2/pathology , Diabetic Angiopathies/pathology , Diabetic Nephropathies/pathology , Kidney/pathology , Arteriosclerosis/physiopathology , Biopsy , Diabetes Mellitus, Type 2/physiopathology , Diabetic Angiopathies/physiopathology , Diabetic Nephropathies/epidemiology , Diabetic Nephropathies/physiopathology , Female , Glomerular Mesangium/pathology , Glomerular Mesangium/ultrastructure , Humans , Incidence , Kidney/physiopathology , Kidney/ultrastructure , Male , Microscopy, Electron , Middle Aged , Models, BiologicalABSTRACT
To determine whether insulin has a vasodilator action on the artery and vein, the effects of insulin at varying concentrations (120 microU/ml, 1.2 mU/ml, 12 mU/ml, and 120 mU/ml) on vasoconstriction by norepinephrine (NE) and angiotensin II (ANG II) were studied in the isolated rabbit femoral artery and vein. Helical strips were suspended in an organ bath filled with modified Krebs solution (pH 7.4), were gassed with 95% O2/5% CO2 at 36 degrees C, and isotonic contractions were measured. Insulin significantly and dose dependently inhibited the vasoconstriction induced by NE (10(-8) M for the artery and 10(-7) M for the vein) at greater than or equal to 1.2 mU/ml for both the artery and vein and the vasoconstriction induced by ANG II (3 x 10(-10) M for the artery and 3 x 10(-9) M for the vein) at greater than or equal to 1.2 mU/ml for the artery and greater than or equal to 12 mU/ml for the vein. The results indicate that insulin has an inhibitory effect on NE- and ANG II-induced contraction in both the artery and vein, and this appeared to be a contributory factor in the hypotensive effect observed in diabetic patients treated with insulin.
Subject(s)
Angiotensin II/pharmacology , Insulin/pharmacology , Norepinephrine/pharmacology , Vasoconstriction/drug effects , Animals , Arteries , Dose-Response Relationship, Drug , Male , Muscle Contraction/drug effects , Muscle, Smooth, Vascular/drug effects , Rabbits , VeinsABSTRACT
The effects of insulin on pressor responsiveness to alpha agonist (phenylephrine) and angiotensin II, and baroreflex function were studied in fifteen diabetic patients without autonomic neuropathy. The dose of phenylephrine required to increase systolic pressure by 25 mmHg (PD25) was significantly increased from 38 +/- 7 to 62 +/- 9 micrograms (p less than 0.05) after IV injection of 4 U of Actrapid monocomponent insulin. The dose of angiotensin II required to increase systolic pressure by 30 mmHg (AD30) was also increased from 0.29 +/- 0.07 to 0.48 +/- 0.10 micrograms (p less than 0.01). Following insulin administration, the dose-response curves for phenylephrine and angiotensin II were shifted to the right. The baroreflex sensitivity was not affected by insulin. In contrast, there was no significant change in PD25, AD30 or baroreflex sensitivity after the injection of saline. These results suggest that insulin attenuates the pressor responsiveness to alpha agonist and angiotensin II, which may be one of the significant mechanisms in insulin-induced vasodilation.
Subject(s)
Diabetes Mellitus/metabolism , Insulin/pharmacology , Pressoreceptors/drug effects , Vasoconstriction/drug effects , Adult , Aged , Angiotensin II/pharmacology , Blood Pressure/drug effects , Diabetes Mellitus/physiopathology , Female , Humans , Male , Middle Aged , Phenylephrine/pharmacology , Pressoreceptors/physiopathologyABSTRACT
Immunohistochemical and electron microscopic examinations were made of a carcinosarcoma of the esophagus in an 80-year-old man. An immunohistochemical examination showed that sarcomatous spindle cells were vimentin-positive, whereas squamous carcinoma cells were keratin-positive. No coexistence of vimentin and keratin in a single tumor cell was found. Electron microscopically, the sarcomatous spindle cells were characterized by well-developed rough endoplasmic reticulum, abundant intermediate filaments, and the occasional presence of peripheral aggregates of microfilaments. No definite desmosomes were identified among these cells. These results appear to indicate that most of the spindle-shaped tumor cells assume fibroblastic cellular features and synthesize the intermediate filament protein usually expressed in mesenchymal cells, even though such tumor cells could be epithelial in origin.