Alpha2-antiplasmin is involved in the production of transforming growth factor beta1 and fibrosis.

BACKGROUND: Fibrotic disease occurs in most tissues. Transforming growth factor (TGF)-beta is the major inducer of fibrosis. The fibrinolytic system is considered to play an important role in the degradation of extracellular matrices. However, the detailed mechanism of how this system affects fibrosis remains unclear. METHODS AND RESULTS: We examined experimental fibrosis in mice with a deficiency of alpha(2)-antiplasmin (alpha2AP), which is a potent and specific plasmin inhibitor. We found that the lack of alpha2AP attenuated bleomycin-induced TGF-beta(1) synthesis and fibrosis. In addition, the production of TGF-beta(1) from the explanted fibroblasts of alpha2AP(-/-) mice decreased dramatically as compared to that in wild-type mice. Moreover, we found that alpha2AP specifically induces the production of TGF-beta(1) in fibroblasts. CONCLUSION: The lack of alpha2AP attenuated TGF-beta(1) synthesis, thereby resulting in attenuated fibrosis. This is the first report to describe the crucial role that alpha2AP plays in TGF-beta(1) synthesis during the process of fibrosis. Our results provide new insights into the role of alpha2AP in fibrosis.

A case of refractory uremic pleuropericarditis--successful corticosteroid treatment.

We report the case of a patient with uremic pleuropericarditis who showed a marked improvement following corticosteroid therapy. A 66-year-old man who had been on hemodialysis therapy for 13 years was admitted to our hospital presenting with increases in bilateral pleural effusions and pericardial effusion. Repeated thoracentesis showed hemorrhagic and exudative findings. Pleural and pericardial fluid cytologic examination, bacterial culture and acid-fast staining showed negative findings. Despite the administration of antibiotics and antituberculosis drugs, low-grade fever continued and C-reactive protein level remained high. A pleural biopsy revealed fibrinous pleuritis without infectious disease or malignancy. He was diagnosed as having uremic pleuropericarditis on the basis of the clinicopathological features, but had been unresponsive to conventional treatments including repeated thoracentesis and the continuance of hemodiafiltration using nafamostat mesylate. Ultimately, both pleural and pericardial effusions were controlled after the treatment with prednisolone at an initial dose of 50 mg per day. In conclusion, corticosteroid therapy seems to be useful for treating patients with conventional therapy-resistant uremic pleuropericarditis.

Rapidly progressive glomerulonephritis in a patient with Chlamydia pneumoniae infection: a possibility of superantigenic mechanism of its pathogenesis.

Herein we describe a case of a patient with rapidly progressive glomerulonephritis after Chlamydia pneumoniae infection. An 88-year-old woman who had had C. pneumoniae infection two months previously was admitted to our hospital with complaints of dyspnea and generalized edema. Laboratory tests revealed acute renal failure, polyclonal hypergammaglobulinemia, highly increased level of C-reactive protein, and hematoproteinuria. A renal biopsy revealed mesangial and endocapillary proliferative glomerulonephritis with crescents. She responded to high-dose steroids, cyclophosphamide, minocycline, and plasma exchange treatment with the remission of oliguric renal failure. The percentage of the subset of CD3+ TCR+ Vbeta11+ cells markedly increased to 9.6% (normal range: < 1.04%) at the onset of the disease and decreased to 0.1% after the treatment. These clinicopathological features were similar to those of superantigen-associated glomerulonephritis after methicillin-resistant Staphylococcus aureus infection. We suggest that the superantigenic mechanism is one of the possible pathomechanisms of this glomerulonephritis.

A case of elderly-onset systemic lupus erythematosus presenting as acute renal failure due to disseminated intravascular coagulation.

Herein we describe a case of a patient with elderly-onset systemic lupus erythematosus presenting as acute renal failure due to disseminated intravascular coagulation. A 78-year-old man was admitted to our hospital with fever and generalized lymphadenopathy. He was diagnosed as having systemic lupus erythematosus on the basis of renal involvement, hematological abnormality and positivity for antinuclear and anti-double-stranded DNA antibodies. Renal biopsy revealed lupus nephritis (class III and V (A/C)) with focal glomerular thrombosis. He responded to hemodialysis and corticosteroid therapy with remission of serological values and renal function. Possible mechanisms underlying the coexistence of these conditions are discussed.

Pressure-induced superconductor-insulator transition in the spinel compound CuRh2S4.

We performed resistivity measurements in CuRh2S4 under quasihydrostatic pressure of up to 8.0 GPa, and found a pressure-induced superconductor-insulator transition. Initially, with increasing pressure, the superconducting transition temperature T(c) increases from 4.7 K at ambient pressure to 6.4 K at 4.0 GPa, but decreases at higher pressures. With further compression, superconductivity in CuRh2S4 disappears abruptly at a critical pressure P(SI) between 5.0 and 5.6 GPa, when it becomes an insulator.

A case of acute renal failure due to rhabdomyolysis, associated with non-autoimmune fulminant type 1B diabetes mellitus.

A 38-year-old man developed severe diabetic ketoacidosis complicated with rhabdomyolysis and acute renal failure after presenting hyperglycemic symptoms for 4 days. Initial investigation showed significant hyperglycemia (blood glucose level 1,593 mg/dl) with a relatively low level of HbA1c (7.0%) and a high pancreatic enzyme concentration without any signs of pancreatitis. Diabetes-related antibodies were absent except for the anti-glutamic acid decarboxylase antibody, which disappeared later on. Pancreatic biopsy examination showed the lack of insulin-secreting cells, without insulitis. These findings were almost consistent with non-autoimmune fulminant type 1B diabetes. The patient remained dependent on dialysis for 1 month, then his renal function recovered. In patients with this type of diabetes, the onset of overt diabetes, frequently accompanied with severe diabetic ketoacidosis, is rapid, hence, early detection, quick diagnosis and immediate treatment of this novel type of diabetes are important in the rescue of these patients.

Endoscopic approach to the pituitary lesions: contemporary method and review of the literature.

The present status of endoscopic transsphenoidal surgery is introduced and reviewed. The difference between endoscopic and microscopic transsphenoidal surgery is explained and also the characteristics of the transnostril approach is mentioned. The advantages of endoscopic surgery are (1) good anatomical orientation with wider view, (2) tumors at the dead angle can be removed under the direct visualization, and (3) the patients can drink, eat and even brush their teeth just after surgery. Short hospital stay and even day-surgery could be possible when a patient is carefully selected. The disadvantages and the limitation of endoscopic surgery have been solved and improved with several new instruments and ideas. Moreover, we have made use of the surgical simulation with the three-dimensional (3-D) CT virtual navigation endoscopic image and the navigation system with the ENT application and the SureTrak of the Stealth Station. There is no need for head fixation with a Mayfield clamp or a C-arm intraoperative fluoroscopic image. This image guidance enabled a correct and smooth approach even in those patients with complicated and abnormal anatomical structures by prior surgery such as for sinusitis. The sellar floor can be safely and correctly opened even in patients with conchal type sphenoid sinus using a navigation system that helps to understand the locations of the cavernous sinus and the internal carotid arteries. The overall result by endoscopic transsphenoidal surgery is as good as or better than that by the traditional microscopic transsphenoidal surgery.

Improved nonpenetrating trabeculectomy with trabeculotomy.

PURPOSE: To examine surgical effects and complications of improved nonpenetrating trabeculectomy with trabeculotomy in glaucoma patients. METHODS: Glaucoma patients in two medical institutions underwent nonpenetrating trabeculectomy with sinusotomy with or without trabeculotomy, and the results were compared retrospectively in the two groups by evaluation of final intraocular pressure, drug score, and occurrence of postsurgical complications. RESULTS: Of the 63 eyes of 51 patients in this study, 31 were treated with nonpenetrating trabeculectomy with sinusotomy without trabeculotomy and 32 eyes were treated with nonpenetrating trabeculectomy with sinusotomy and trabeculotomy. The mean follow-up period was 17.0 months. The clinical features in both groups were similar in terms of age, presurgical intraocular pressure (P = 0.96), and presurgical drug score. The eyes treated with nonpenetrating trabeculectomy with sinusotomy without trabeculotomy had significantly reduced intraocular pressures from 21.0 +/- 4.3 (mean +/- SD) to 15.8 +/- 6.3 mm Hg (P = 0.0003) and drug scores from 2.4 +/- 1.2 to 1.6 +/- 1.1 without postsurgical complications. The eyes treated with nonpenetrating trabeculectomy with sinusotomy and trabeculotomy had significantly reduced intraocular pressures from 22.3 +/- 7.5 to 12.5 +/- 2.3 mm Hg (P < 0.0001) and drug scores from 2.5 +/- 1.9 to 0.9 +/- 1.3 without postsurgical complications. Thus, the eyes treated with nonpenetrating trabeculectomy with sinusotomy and trabeculotomy had significantly lower intraocular pressures (P = 0.016) and drug scores than did those treated with nonpenetrating trabeculectomy with sinusotomy without trabeculotomy. CONCLUSION: The authors obtained satisfactory results in reducing intraocular pressure by the combination of nonpenetrating trabeculectomy, sinusotomy, and trabeculotomy.

Role of galactosylation in the renal pathogenicity of murine immunoglobulin G3 monoclonal cryoglobulins.

Cryoglobulin activity associated with murine immunoglobulin G3 (IgG3) has been shown to play a significant role in the development of murine lupuslike glomerulonephritis. A fraction, but not all, IgG3 monoclonal antibodies are capable of inducing a severe acute lupuslike glomerulonephritis as a result of direct localization of IgG3 cryoglobulins, suggesting the importance of qualitative features of cryoglobulins in their nephritogenic activities. Here a remarkable difference is shown in the renal pathogenicity of 2 murine IgG3 monoclonal cryoglobulins, identical in the amino acid sequences of their heavy and light chains but different in galactosylation patterns of oligosaccharide side chains because of their synthesis in different myeloma cells. The antibody lacking the capacity to induce severe glomerulonephritis displayed an increased proportion of galactosylated heavy chains. Changes in conformation, as revealed by gel filtration analysis, reduced cryoglobulin activity, and accelerated clearance could account for the lack of the renal pathogenicity of the more galactosylated variant. This observation provides a direct demonstration for the role of IgG galactosylation in the pathogenic potential of cryoglobulins. (Blood. 2001;97:3537-3543)

[Radiation induced glioblastoma: a case report].

We report a surgical case of a 54-year-old woman with a radiation induced glioblastoma. At the age of 34, the patient was diagnosed to have a non-functioning pituitary adenoma. It was partially removed followed by 50 Gy focal irradiation with a 5 x 5 cm lateral opposed field. Twenty years later, she suffered from rapidly increasing symptoms such as aphasia and right hemiparesis. MRI showed a large mass lesion in the left temporal lobe as well as small mass lesions in the brain stem and the right medial temporal lobe. These lesions situated within the irradiated field. Magnetic resonance spectroscopy revealed relatively high lactate signal and decreased N-acetyl aspartate, choline, creatine and phosphocreatine signals. Increased lactate signal meant anaerobic metabolism that suggested the existence of a rapidly growing malignant tumor. Thus, we planned surgical removal of the left temporal lesion with the diagnosis of a radiation induced malignant glioma. The histological examination revealed a glioblastoma with radiation necrosis. MIB-1 staining index was 65%. Postoperatively, her symptoms improved, but she died from pneumonia 1 month after the surgery. An autopsy was obtained. The lesion of the left temporal lobe was found to have continuity to the lesion in the midbrain, the pons and the right temporal lobe as well. High MIB-1 staining index suggested that a radiation induced glioblastoma had high proliferative potential comparing with a de novo and a secondary glioblastoma.

[New ideas for indirect revascularization surgery for moyamoya disease].

We had performed indirect revascularization surgery, mainly EMS, for cases with moyamoya disease, because EMS can revascularize a large area including the territory of anterior cerebral artery. However, in our initial cases, we found that three sides in two cases had post-operative ischemic complications. These cases suggested that intracranial hypertension due to pressure exerted by swelling caused by edema in the myoflap after EMS was one of the reasons for these infarctions. For the prevention of intracranial hypertension due to the edema in the myoflap, when we did EDAMS with dural pedicle insertion, we put into practice the new ideas about shaving the boneflaps to half of their original thickness, and prescribed 20% Mannitol after surgery. We tried these new ideas concerning treatment on four sides in three cases with moyamoya disease, and we were able to get good outcomes without any new neurological deficits.

Removal of petrous apex meningioma and microvascular decompression for trigeminal neuralgia through the anterior petrosal approach. Case report.

A 64-year-old female presented with right trigeminal neuralgia. Computed tomography and magnetic resonance (MR) imaging demonstrated a tumor attached to the right petrous apex. MR imaging also revealed that the trigeminal nerve was compressed and distorted by the tumor. Tumor removal and microvascular decompression (MVD) were performed via the anterior petrosal approach. The trigeminal nerve was distorted by the tumor and the superior cerebellar artery compressed the medial part of the root entry zone of the trigeminal nerve. The surgery resulted in complete relief of the trigeminal neuralgia. Posterior fossa tumors causing ipsilateral trigeminal neuralgia are not rare, and are often removed via the suboccipital retromastoid approach, as MVD for trigeminal neuralgia is usually performed through the retromastoid approach. The advantages of the anterior petrosal approach are shorter access to the lesion and direct exposure without interference from the cranial nerves, and that bleeding from the tumors is easily controlled as the feeding arteries can be managed in the early stage of the surgery. We conclude that the anterior petrosal approach is safe and advantageous for the removal of petrous apex tumor associated with trigeminal neuralgia.

[A case of tuberous sclerosis presenting intractable adversive seizure, successfully resected with the technique of "gyrectomy"].

We report a 9-year-old girl with tuberous sclerosis presenting intractable adversive seizure. She had been suffering from frequent attacks of consciousness loss since the age of 6 years. Although a considerable amount of antiepileptic drugs had been administered, her epileptic attacks were not controlled, but instead rather increased. She had been suffering from adversive seizure to the right for more than 2 years. CT scan failed to show any abnormal density area. MRI showed a small lesion in the left frontal subcortical area. The electroencephalogram showed relatively mild abnormal waves in the left hemisphere. We undertook surgical removal of the lesion with epileptogenic foci because her epilepsy has not been controlled and the lesion could be a glioma. Abnormal spike waves were detected around the lesion with electrocorticogram. "Gyrectomy" technique was employed and the spike waves totally disappeared. After the surgery, no neurological deterioration was presented. She has suffered no seizure attack since the surgery even though the amount of the antiepileptic drugs has been significantly decreased. Resection of the epileptogenic foci as well as the abnormal lesion using the technique of gyrectomy is useful for the control of the intractable epilepsy, and makes the quality of life of patients much higher.

[The EMG findings of spasmodic torticollis--the character of the EMG findings of neurogenic torticollis].

Spasmodic torticollis is a clinical entity that is hard to treat though various symptomatic therapy have been tried. On the other hand, microvascular decompression operation have been established for cranial nerve vascular compression syndrome such as hemifacial spasm. Case reports on the decompression of the spinal accessory nerve for the treatment of spasmodic torticollis have been published on the basis of the concept of cranial nerve vascular compression syndrome. Thus, spasmodic torticollis related to unilateral accessory nerve has attracted much attention for selecting an optimal treatment, although there have not been any diagnostic criteria with electromyographic study. From the viewpoint of the clinical electrophysiological findings on hemifacial spasm those we have acquired by EMG study, we have examined the EMG findings of various types of spasmodic torticollis and here report the classification of spasmodic torticollis based on the EMG study. Thirty-five patients with spasmodic torticollis were analyzed. The symptoms were classified to the horizontal rotation type, the lateral bending type and the mixed type with the number of each group of 23, 2 and 10, respectively. As we have shown the criteria of the EMG findings on hemifacial spasm, the EMG of the patients with spasmodic torticollis were analyzed on four conditions as follows; (1) distribution of the involved muscles, (2) maximum firing rate of the abnormal spontaneous activity of the sternocleidomastoid muscle, (3) synkinetic discharge between the muscles innervated by unilateral accessory nerve and (4) alteration of the spontaneous muscle discharge by posture change. Abnormal spontaneous muscle discharges were recorded only from the sternocleidomastoid muscle and the trapezius muscle on the same side in twelve patients. Maximum firing rate of spontaneous muscle discharge was higher than that of maximum voluntary contraction in twenty-two patients. Abnormal synkinetic discharge was recorded between the sternocleidomastoid muscle and the trapezius muscle on the same side in twenty-one patients. Spontaneous EMG activities of the muscles innervated by the accessory nerve increased when the patients stood up from the resting supine position in thirty-one patients. Thus, ten patients out of thirty-five subjects had all four conditions mentioned above as typical patients with hemifacial spasm usually had. These ten patients with spasmodic torticollis were thought to have strong similarity to the EMG characteristics of hemifacial spasm that suggested hyperexcitability of unilateral accessory nervous system. This classification with EMG is considered to be useful in diagnosing the spasmodic torticollis related to unilateral accessory nerve and can be applied for selecting an optimal treatment.

[An operative case of cholesterol granuloma of the petrous apex].

A 59-year-old man presented with a rare cholesterol granuloma of the petrous apex manifesting as headache, left facial dysesthesia, diplopia, left hearing impairment, and left tinnitus. Neurological examination revealed dysesthesia of territory in all divisions of the left trigeminal nerve, left incomplete abducens nerve palsy, left mixed hearing impairment, and left tinnitus. Plain CT scan showed a smoothly marginated mass involving the left petrous apex. The mass was isodense with the brain parenchyma and not enhanced by contrast medium. The mass appeared heterogeneously slightly hyperintense on the T1-weighted MR image and homogeneously hyperintense on the T2-weighted MR image except for the peripheral portion. The mass was not enhanced after intravenous gadolinium DTPA administration. Surgery via a petrosal approach totally removed the mass in the intracranial, extradural space. Histological examination showed typical features of cholesterol granuloma, with cholesterin clefts, hemosiderin deposits, and erythrocytes in non-specific granulation tissue. Cholesterol granuloma most commonly occurs in the middle ear cavity, and rarely in the petrous apex. The characteristic hyperintense appearance of cholesterol granuloma on T1- and T2-weighted MR images is very useful for differentiation from other lesions of the petrous apex and the cerebellopontine angle such as cholesteatoma, mucocele, chordoma, and meningioma. Solid cholesterol granuloma of the petrous apex should be treated by total removal via craniotomy, not by drainage which is commonly performed by otorhinologists.

Microsurgical anatomy around the foramen of Luschka in relation to intraoperative recording of auditory evoked potentials from the cochlear nuclei.

Three cadaveric heads were dissected to investigate the microsurgical anatomy around the foramen of Luschka. It was found possible to place a recording electrode in proximity to the cochlear nuclei by inserting it in the lateral recess of the fourth ventricle through the foramen of Luschka. In operations of the cerebellopontine angle using the retromastoid approach, access to the foramen of Luschka and the lateral recess is obtained by retracting the biventral lobule of the cerebellum in a caudal-rostral direction under a caudal-rostral/medial field of vision. The craniectomy might need to be enlarged a few millimeters in the caudal direction. A wick electrode can be inserted in the lateral recess beneath the choroid plexus in a rostromedial direction and to a depth of approximately 3 to 5 mm from the foramen of Luschka without excessive retraction of the cerebellum. The optimum position for the recording electrode is in the triangle formed by the axis of the cochlear nerve and the glossopharyngeal nerve and by the lip of the foramen of Luschka. The caudal retromastoid approach is more suitable than the translabyrinthine technique for recording from the cochlear nuclei as well as for implantation of stimulating electrodes into the cochlear nuclei for use as hearing prostheses.