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The role of Epstein-Barr virus (EBV) reactivation in the pathogenesis of Vogt-Koyanagi-Harada (VKH) disease was examined.Using B lymphocytes obtained from 8 patients with VKH disease and 10 patients with other types of uveitis, immortarized lymphoblast lines were established and infected with EBV. The degree of EBV activation in each lymphoblast line, in the presence and absence of various stimuli, was assessed by measuring the expression of 3 different antigens involved in replication by immunofluorescent staining and western blot analysis. Quantification of EBV DNA in cell culture supernatants was done by polymerase chain reaction.Cell lines established from VKH patients expressed more viral antigens that those established from patients with other types of uveitis. There were greater amounts of EBV DNA in the VKH cell lines.B lymphocytes from VKH patients may be more susceptible to EBV activation, and the reactivation of EBV may be involved in the pathogenesis of VKH.

The patient was a 51-year-old man with Marfan syndrome who had simultaneously undergone modified Bentall operation (Carrel patch method) and coronary artery bypass grafting. Prosthetic valve endocarditis (PVE) occurred 19 months after the operation. PVE had thereafter been treated by antibiotic therapy for 3 months, but echocardiography revealed prosthetic valve detachment and aortic root pseudoaneurysm ruptured into the right ventricle which appeared to have been caused by PVE. At reoperation there were no laboratory or intraoperative findings indicative of ongoing inflammation or infection. The composite graft, therefore, didn't require replacing, and it was possible to simply re-suture the composite graft and directly close the tear. The postoperative course has been uneventful with no further evidence of endocarditis.

To elucidate the possible role of pancreatic juice reflux into the biliary tract in promoting the development of biliary carcinoma, Syrian hamsters were subjected to cholecystoduodenostomy and ligation of the distal end of the common duct and then subcutaneously injected with N-nitrosobis(2-oxopropyl)amine (BOP) (experimental group). The incidences of gallbladder carcinoma and extrahepatic bile duct carcinoma in the experimental group was significantly higher than in the sham-operated group (P0.01, P0.05). The proliferating cell nuclear antigen (PCNA) labeling indices of both regions gradually increased with time, and were significantly higher in the experimental group at weeks 9 and 16 than in the sham-operated group at the same time. Trypsin and phospholipase A2 (PLA2) activities in bile and tissue levels of superoxide dismutase (SOD) in the gallbladder and extrahepatic bile ducts were higher in the experimental group than in the sham-operated group. These findings suggest that the carcinogenic effect of BOP was enhanced in biliary epithelium that had proliferated in response to and/or had been injured by activated pancreatic enzymes refluxing into the biliary tract and then increased free radical activity, leading to a high frequency of carcinoma development in the biliary tract.

We have fabricated low loss multimode polymeric optical waveguides with high thermal stability for a parallel optical interconnect module using UV cured epoxy resins. The propagation loss of the waveguide at 830 nm was 0.08 dB/cm and no increment was observed after a solder bumps melting test.

Endotoxin (lipopolysaccharide: LPS) infection due to bacterial translocation is intimately involved in the organ failure that occurs after highly invasive interventions such as extensive liver resection, and has attracted a great deal of interest. LPS that has translocated into portal blood binds to LPS-binding protein (LBP) and is transported to the monocytes and Kupffer cells in liver sinusoids where it is activated through the soluble CD14 that is present on their cell membranes or in blood plasma. Inflammatory cytokines such as TNF-alpha and IL-6 are produced and released by monocytes and Kupffer cells that have been activated by LPS-LBP complexes, and the endothelial cell of the sinusoids is damaged by these inflammatory cytokines. The original anticoagulant function of the damaged endothelial cells is reduced, and microcirculatory insufficiency is caused by the formation of microthrombi. It is important to understand this network mechanism and to prevent invasion, and attention has recently been focused on LBP and CD14 because of this point. The increase in LPS as a result of extensive liver resection, which is highly invasive, begins 3 hours after surgery, and peaks at 6 hours. LBP, however, is awaiting the entry of LPS, principally in the periportal hepatocytes. Its production peaks at 12 hours, and this is related to the excessive production of inflammatory cytokines have been produced, expression of LBP must be suppressed within 12 hours to inhibit this excessive reaction, and that will be the task of a future study.

Heat-shock protein 60 derived from Yersinia enterocolitica (Yersinia HSP 60) and bovine retinal HSP (Retina HSP 60) were previously identified by immunological cross-reaction and a high degree of common antigenicity, and a specific antibody against both proteins was detected in the sera of uveitis patients. We report here an attempt to isolate and purify Retina HSP 60 and Yersinia HSP 60. Both Retina HSP 60 and Yersinia HSP 60 showed an enriched content of glycine of approximately 60 to 80%. Lewis rats were inculated with 50 or 100 micrograms of purified Retina or Yersinia HSP 60 emulsified in complete Freund's adjuvant. In 50 to 60% of those inoculated with Retina HSP 60, uveoretinitis was observed about 13 days after inoculation, with massive infiltration of lymphocytes and polymorphonuclear neutrophils in the iris, ciliary body, and retinal tissue. Rats inoculated with Yersinia HSP 60 did not develop ocular inflammation. Lymphocyte proliferation assay was performed to investigate cellular immunoresponses in the rats that developed ocular inflammation after immunization with Retina HSP 60. The results showed significantly higher response to the Retina and Yersinia HSP 60 than to either S-antigen or interphotoreceptor retinoid-binding protein (IRBP), which are known to induce ocular inflammation. Cross-reaction between Retina and Yersinia HSP 60 is suggested. This study suggests that the HSP 60 molecules may be involved in the pathogenesis of intraocular inflammation.

We made cone sensitivity measurements and hue discrimination measurements in 58 eyes of 34 diabetic patients with and without diabetic retinopathy including preproliferative retinopathy. The same measurements were performed in 8 eyes of 8 subjects to compare them. In this study, we were able to make the measurements in a short time and comfortably for the patients because we only needed to measure peak sensitivities of spectral sensitivity curves in three cones. There was significant correlation between short wave length sensitive-cone pathway sensitivity and retinopathy levels determined by fluorescein angiography. The cone sensitivity measurements that we used in this study were simple and sensitive. Our results suggested that the measurements were useful for detection of visual functional disturbances, determination of retinopathy levels, and prognosis.

Thrombomodulin (TM) is a protein, present on intact endothelial cell surfaces, that plays a major role in the protein C anticoagulant system. Plasma TM is produced by injured endothelium, and is recognized in circulating blood or urine as a sign of endothelium cell damage. The localization of TM within the eye and its kinetics in the eye and the serum were investigated in rats with experimental autoimmune uveoretinitis (EAU). An immuno-histochemical study showed the presence of TM at sites of fibrin in the anterior chamber and retinal vasculitis. The amount of TM in the eye increased with progression of intraocular inflammation, but the serum level of TM did not significantly differ from the values in the control group. These data suggest that TM may play a role in preventing thrombosis in cases of vasculitis and fibrin formation in the anterior chamber in EAU, thus maintaining blood flow and the fluidity of aqueous humor.

Cytomegalovirus (CMV) retinitis is the most common intraocular infection in patients with Acquired immunodeficiency syndrome (AIDS). Approximately 25% of patients with AIDS will develop CMV retinitis during their life time. It is generally associated with CD4+ lymphocyte counts of less than 50 cells/microliter. Clinically, the most characteristic feature of CMV retinitis is a yellow-white lesion of retinal necrosis with a granular border extending into the surrounding retina. At present, ganciclovir and foscarnet have been approved for the treatment of CMV retinitis in patients with AIDS. Although both drugs arrest the progression of retinitis, relapse often occurs. More than ever, ophthalmologists have a special obligation to alleviate both the physical and psychological suffering of patients with CMV retinitis.

Neurosteroids are de novo synthesized in the nervous system through mechanisms at least partly independent of peripheral steroidogenic glands. However, the concept of neurosteroidogenesis in neurons is not clear in mammalian brains. The present study identified the presence of cytochrome P450scc in the rat Purkinje cell, a typical cerebellar neuron. Immunohistochemical analysis with the antibody against the purified bovine adrenal P450scc showed an immunoreaction restricted to somata and dendrites of the Purkinje cells in adult cerebella. Preadsorbing the antibody with P450scc resulted in a complete absence of the immunoreaction. The antibody against inositol triphosphate receptor, a marker of the Purkinje cell, recognized P450scc-immunoreactive cerebellar cells that showed no immunoreaction with glial fibrillary acidic protein, a specific marker of glial cells. Expression of the P450scc-like protein in the cerebellum was verified by Western blot analysis, and cerebellar P450scc messenger RNA, by RT-PCR analysis in adulthood. On the other hand, P450scc-immunoreactive cells were found to scatter throughout the cerebellum at 0 day of age, before the differentiation of the first Purkinje cells, while the site of expression of this protein was localized only in somata of Purkinje cells at 3 days of age. Immunoreactive dendrites of the Purkinje cell spread into the molecular layer during neonatal development concurrently with its maturation. The intensity of the immunoreaction did not change during neonatal life. Expression of the cerebellar P450scc messenger RNA was also detected after birth, and the level was almost constant during neonatal life. A specific RIA indicated that the pregnenolone concentration was unexpectedly high at 0 day and decreased until 7 days. The total amount of pregnenolone in the cerebellum was almost constant from 0-7 days and increased during 7-21 days concurrently with the cerebellar development. In contrast, the pregnenolone sulfate ester level was low and did not significantly change among the developmental stages. These results suggest that steroidogenic enzyme P450scc appears in the rat Purkinje cell immediately after its differentiation. The expression of this enzyme may remain during neonatal development and in adulthood.

Experimental autoimmune uveoretinitis (EAU) in mice, an organ specific autoimmune disease, has been investigated as an animal model for human endogenous uveitis. In this study, we report on the immunosuppressive effect of transforming growth factor-beta 1 (TGF-beta 1) on the development of EAU in mice. Inhibition by TGF-beta 1 of proliferation of interphotoreceptor retinoid-binding protein (IRBP)-specific T cell lines in B10.A mice against IRBP antigen was dose-dependent. However, when spleen cells used as the antigen presenting cell were first cultured with TGF-beta 1, this anti-proliferation effect was abolished. When IRBP-immunized mice were injected intraperitoneally with TGF-beta 1, dose-dependent suppression of EAU was obtained. The proliferation response of lymph node cells from TGF-beta 1 injected mice with IRBP-induced EAU was suppressed compared with phosphate buffered saline (PBS)-injected mice. These findings suggest that TGF-beta 1 may be a cytokine that plays a role in suppressing IRBP induced EAU in mice.

We have developed a method for quantifying the complexity of activation patterns observed during ventricular fibrillation (VF) that is based on our previously reported methodology for decomposing epicardial mapping data into a set of isolated wavefronts. One-half second datasets are acquired from a 21 x 24 array of unipolar electrodes (1 mm spacing), and the wavefronts are isolated. A correlation technique is used to compute the similarity between all possible pairs of the isolated wavefronts. From these data, the wavefronts are sorted into clusters, each of which represents a recurring wavefront morphology. We define multiplicity (M) as the number of clusters needed to account for 90% of the total activations in the VF episode. M measures the complexity of the rhythm. In repetitive patterns (e.g., sinus rhythm), M = 1, indicating that the same morphology repeatedly activates the mapped region. Typically, in VF, M > 1, with larger numbers representing more complex, disorganized patterns. As an example, we computed M at 5, 10, 15, and 20 sec after electrical induction of VF in six pigs. M decreased significantly (p < 0.001), suggesting increasing organization during this period.

We encountered three cases of thymic hyperplasia associated with hyperthyroidism. Case 1 was in a 35-year-old woman; a chest CT scan showed an anterior mediastinal mass and right-sided pleural effusion, which suggested the presence of a thymoma Case 2 was in a 21-year-old man who complained of palpebral ptosis and also had myasthenia gravis (Osserman type I). Case 3 was in a 47-year-old woman; a chest CT scan showed thymic hyperplasia and mediastinal lymphadenopathy. In all cases, anti-thyroid medication was given first, because of the associations with hyperthyroidism. Moreover, in cases 1 and 2 no tumor was found, and only hyperplasia was detected in the thymus, although both patients underwent extended thymectomy. Furthermore, surgery was not effective against the hyperthyroidism (anti-thyroid medication could not be withdrawn or reduced). In cases 2 and 3, thymic hyperplasia, as seen on chest CT scans, resolved as thyroid function was normalized by anti-thyroid medication. The pretracheal lymphadenopathy seen in case 3 also resolved. Thymic hyperplasia may have been a result, not a cause, of hyperthyroidism. When we encounter patients with thymic masses and hyperthyroidism, we should give anti-thyroid medication and observe the thymus for some time before resorting to surgery.

A person of advanced age usually has degenerative changes of bone, joint and ligament, which can be causes of cervico-omo-brachial pain and disability. He or she may also suffer from metastatic bone tumor of cervical spine or upper extremity. This article described pathology, signs and symptoms and recent treatment of these diseases. Cervical myelopathy and radiculopathy, which are most common causes of cervico-omo-brachial symptoms, are sometimes accompanied by peripheral entrapment neuropathy such as cubital tunnel syndrome or carpal tunnel syndrome (double crush syndrome). In this complicated situation, decompression of neural tissue in both cervical spine and carpal tunnel are necessary. In treatment for carpal tunnel syndrome, release of transverse carpal ligament under an arthroscope has proven to be useful and has been becoming popular. This minimally invasive surgery is also useful in shoulder surgery such as subacromial decompression in aged patients with rotator cuff tear and removal of calcium deposit in the shoulder joint. Osteoarthritis of the elbow also cause pain or disability of the elbow and the hand. Some metastatic bone tumors are treated by tumor resection and reconstruction with instruments, prosthesis or composite grafts, which are attempted not to cure the disease but to maintain or improve the quality of life of the patient.

Skin allotransplantation in rats were rejected even if they were treated with a suboptimal dose of FK506. However, skin allograft in rats which received vascularized limb allograft simultaneously were rejected more slowly. We hypothesized this prolongation phenomenon was due to a continuous supply of donor-derived progenitor cells from a vascularized bone marrow. In the present study, we compared the mean survival times (MSD) of skin allograft in rats that were simultaneously received nonirradiated rat limb, irradiated rat limb, or bone marrow cells.

Five patients presenting with chronic dorsal wrist pain and diagnosed as distal posterior interosseous nerve syndrome are reported. Clinical examination revealed point tenderness of the fourth extensor compartment. The symptoms were reproduced by extreme wrist extension in all patients and by extreme flexion in three of the patients. The pain was relieved in all patients by a selective lidocaine block of the terminal branch of the posterior interosseous nerve at the wrist joint. All the patients failed to respond to nonoperative treatment and underwent surgical exploration of the nerve. The operative findings were an enlarged nerve in three patients and adhesion of the nerve to the joint capsule in five patients. A 2 cm section of the nerve proximal to the extensor retinaculum was resected. Four of the five patients had excellent pain relief and returned to full asymptomatic activity. One patient had improvement in pain and was satisfied with the outcome. A diagnosis of distal posterior interosseous nerve syndrome should be considered if the usual sources of dorsal wrist pain are eliminated.

Sympathetic ophthalmia (SO) is very rare but it remains one of the most intractable eye diseases. In clinical manifestations and histopathologic features SO is known to resemble closely Vogt-Koyanagi-Harada's disease (VKH disease). We had reported that VKH disease was significantly associated with HLA-DRB1*04 and -DQB1*04 in Japanese patients. In this study, to investigate an HLA association with SO we performed HLA serological and PCR-based DNA typing in 16 patients and 50 healthy controls. Our study revealed that HLA-DRB1*04 (0405; Pc < 5 x 10(-4)), DQA1*03 (Pc < 5 x 10(-3)), and DQB1*04 (0401; Pc < 5 x 10(-4)) were significantly associated with SO as compared to the healthy controls but there was no significant difference in the frequencies of any DPB1 alleles between the patients and healthy controls. It can be postulated that not only the clinical manifestations but also the genetic predisposition of SO are very similar to those of VKH disease.

Two of three brothers (the second and third brothers) and their uncle (their mother's brother) presented acrogigantism without multiple endocrine neoplasia type 1 (MEN 1). An invasive macroadenoma was found in the second brother, and it was histologically confirmed as a sparsely granulated GH cell adenoma. Two distinct microadenomas were found in the third brother, and these were histologically diagnosed as a mixed GH cell and PRL cell adenoma and a sparsely granulated GH cell adenoma, respectively. The loss of heterozygosity (LOH) was analyzed in two adenomas (GH cell adenoma from the second brother and a mixed GH cell and PRL cell adenoma from the third brother) by determining microsatellite polymorphisms of DNAs from tumors and patients' leukocytes. The LOH was found on the chromosome 11q13, whereas LOH was not detected on 1p31-36, 2p, 3p, 4, 5, 6p, 7, 8, 9p21-22, 12p, and 19q13 in both pituitary adenomas examined. The haplotype analysis showed that the same haplotype on 11q13 was found in their mother and the unaffected first brother as well as in the affected uncle and two brothers. The deleted alleles on chromosome 11q13 in the tumors of two affected brothers were, however, restricted to those transmitted from their unaffected father. These data suggest that inactivation of the MEN 1 gene or other tumor suppressor genes on chromosome 11q13 plays an important role for the development of our familial acrogigantism without MEN 1.

We reported a case of a 70-year-old female who underwent simultaneous carotid endarterectomy and coronary artery bypass surgery. Preoperatively, cardiac catheterization demonstrated three vessel coronary artery disease. Her carotid angiogram revealed a 90% stenosis in the left common carotid artery. The cerebral blood flow scintigram on acetazolamide stress detected severely reduced cerebral blood flow on her left anterior and temporal lobe. Her postoperative course was uneventful. Postoperatively, no reduced cerebral blood flow was detected on the acetazolamide stress image. In patients with significant carotid artery stenosis, the cerearal blood flow scintigraphy on acetazolamide stress was a useful method for the simultaneous carotid endarterectomy and coronary artery bypass surgery.

A 43-year-old female was hospitalized on October 25, 1993, due to severe back pain. She was diagnosed with annulo aortic ectasis, Stanford type-A acute aortic dissection and pectus excavatum caused by Marfan's syndrome. On November 30, 1993, single-stage surgery was performed, including modified Bentall procedure, aortic arch replacement, elephant trunk method and sternoplasty. Concerning the procedure for pectus excavatum, sternoplasty was selected because we thought that sternoplasty could endure the long procedure which would cause infection compared with sternal turnover. Postoperative course was satisfactory, and she is well 18 months after surgery.

Mapping After Monophasic and Biphasic Shocks. Introduction: The reason for the increased defibrillation efficacy of biphasic shocks over monophasic shock is not definitely known. Methods and Results: In six anesthetized pigs, we mapped the epicardium after transvenous defibrillation shocks to compare the activation patterns following successful biphasic shocks with unsuccessful monophasic shocks of the same voltage. The heart was exposed and a 510-electrode sock with approximately 4-mm interelectrode spacing was pulled over the entire ventricular epicardium and sutured to the pericardium. Defibrillation catheters were placed in the right ventricular apex and in the superior vena cava. Paired monophasic 12 msec and biphasic 6/6 msec defibrillation shocks were given using an up-down protocol to keep shock strength between the defibrillation thresholds for the two waveforms so that the biphasic shock was successful while the monophasic shock was not. Activation fronts immediately following 60 paired shocks were recorded and analyzed by animated maps of the first derivative of the electrograms. The ventricles were divided into apical (I), middle (II), and basal (III) thirds, and early sites, i.e., the sites from which activation fronts first appeared on the epicardium following the shock, were grouped according to their location. Postshock intervals, i.e., the time from the shock until earliest epicardial activation occurred, were also determined. No ectopic activation fronts followed the shock in 20 biphasic episodes. In the other 40 paired episodes, the number of early sites was smaller after biphasic shocks than after monophasic shocks (monophasic: 198 (total), 3.3 ± 0.9 (mean ± SD) per shock episode; biphasic: 67, 1.1 ± 1.0, P < 0.05]. For biphasic but not monophasic shocks, early sites were less likely to arise from the middle (II) and basal (III) thirds than from the apical third (I) [monophasic: I: 84 (42%), II: 68 (34%), III: 46 (23%); biphasic: I: 49 (73%), II: 10 (15%), III: 8 (12%), P < 0.05]. Postshock intervals were significantly shorter for monophasic shocks (54 ± 14 msec) than for biphasic shocks (75 ± 23 msec, P < 0.05). Conclusion: The decreased number of activation fronts and the longer delay following the shock for the earliest epicardial appearance of those activation fronts that do occur may be responsible for the increased defibrillation efficacy for biphasic shocks.

Coronary artery bypass grafting (CABG) for ischemic heart disease associated with acromegaly has never been reported in Japan, though coronary artery sclerosis is known as complicating factor in acromegaly. A 44-year-old man with ischemic heart disease was admitted to our hospital and emergency percutaneous transluminal coronary recanalization was performed. After admission, he was diagnosed as acromegaly from endocrinological studies and operated on CABG. The peri- and post-operative course was uneventful in spite of our fear for complications due to acromegalic heart muscle disease.

A 34-year-old man with hypertension and diabetes mellitus developed dizziness and visited our institute. He had history of headache with numbness of the right hand since age 15 years and left occipital lobe infarction at age 28 years. The cerebral angiogram showed several changes peculiar to advanced stage of moyamoya disease (spontaneous occlusion of the circle of Willis), i.e. segmental stenoses or occlusions of bilateral internal carotid arteries, left vertebral artery and left posterior cerebral artery with abnormal vascular networks at the bilateral basal ganglia. He was also diagnosed to have asymptomatic ischemic heart disease. The coronary angiogram showed diffuse sclerotic lesions of left anterior descending and right coronary arteries without significant stenosis, which suggested the presence of microvascular lesion as a cause of myocardial ischemia. Coronary disease has been rarely reported as a complication of moyamoya disease, and microvascular coronary artery disease has never been described. Moyamoya disease should be regarded as a part of systemic vascular disorders, and the evaluation of extracerebral cardiovascular system is necessary to clarify pathophysiology of this disease.

A case of Pneumocystis carinii (P. carinii) choroidopathy is reported. The patient was a 17-year-old man with acquired immunodeficiency syndrome (AIDS) who developed bilateral, multifocal, yellow-white, round, flat choroidal lesions ranging in size from 1/8 to 1/6 of the disc diameter while undergoing treatment for cytomegalovirus retinitis. He had had P. carinii pneumonia 43 months previously, and received inhaled pentamidine as suppressive therapy. Over a 4-week period of observation, the choroidal lesions appeared to enlarge slowly and increased in number in the posterior pole, with no clinical evidence of intraocular inflammation and retinal involvement. He was diagnosed as having P. carinii choroidopathy and treated with intravenous pentamidine. Three months after systemic pentamidine therapy was begun the choroidal lesions disappeared. Despite the fact that P. carinii choroidopathy is a rare opportunistic ocular infection, ophthalmic manifestations may be an important initial marker of extrapulmonary disseminated infection in some patients. Therefore we recommend ophthalmologic examinations in patients with AIDS who receive long-term aerosolized pentamidine prophylaxis for pneumonia.

We evaluated an enzyme-linked immunosorbent assay test (Adenoclone) for the rapid diagnosis of adenovirus infection in 589 cases of acute follicular conjunctivitis. Of 255 cases of adenoviral conjunctivitis proven by positive virus isolation. Adenoclone was positive in 51.0% by visual determination and 40.4% by spectrophotometry. Twenty-seven of 130 cases giving visually positive results were interpreted to be negative by spectrophotometry. In 334 adenovirus-negative cases, Adenoclone was negative in 99.1% and 99.4 by visual and spectrophotometric determination, respectively. Adenoclone was less sensitive in cases of adenovirus 3, 4 or 37, infections than in those of adenovirus 8, and also showed lower sensitivity in cases presenting mild conjunctivitis. Adenoclone is a rapid and easy test with high specificity but low sensitivity, and thus the test seems to be helpful in diagnosing adenoviral conjunctivitis.

We reviewed the records of 980 patients with endogenous uveitis who were followed in the uveitis clinic of the Tokyo Medical College Hospital, Department of Ophthalmology. A group of 693 patients examined within a 5-year period from January, 1989 through December, 1993 (Group A) were compared to an earlier group of 287 patients examined within a 3-year period from January, 1982 through December, 1984 (Group B). The incidence of Behçet's disease, intermediate uveitis, and toxoplasmosis showed an apparent decrease. In contrast, the incidence of sarcoidosis and acute anterior uveitis increased. In comparison to Group B, Group A showed an increased number of patients with virus-associated uveitis, toxocariasis, and uveitis caused by fungal infection. The changes observed in the prevalence of certain uveitic diseases in the patient population we followed may be related to changing environment and/or life style, in addition to various advances in diagnostic testing. In the future, the classification of uveitis will become more varied according to the establishment of new concepts.

To test whether fatal deterioration of defibrillation efficiency during antiarrhythmic therapy can be prevented by avoiding extreme decrease in ventricular prevented by avoiding extreme decrease in ventricular conduction or toxic plasma drug levels, we determined the defibrillation threshold (DFT) before and during infusion of incremental doses of disopyramide (n = 8), mexiletine (n = 9), or flecainide (n = 9) in anesthetized dogs. Disopyramide did not alter DFT [from 4.4 +/- 1.5 to 4.4 +/- 1.6 J (3.1 +/- 1.2 micrograms/ml)]. Mexiletine tended to increase DFT [from 4.6 +/- 1.2 to 6.1 +/- 2.0 J (1.8 +/- 0.6 micrograms/ml); p0.05], and defibrillation eventually was unsuccessful in 3 of the 9 dogs. Although the plasma mexiletine level before refractory fibrillation was far beyond the human therapeutic range, prolongation of intraventricular conduction time (CT) was moderate (16 +/- 3%). Flecainide increased DFT from 4.2 +/- 1.3 to 6.1 +/- 1.5 J at a plasma level of 1.04 +/- 0.37 micrograms/ml (p0.0005). In 3 of 5 dogs that developed refractory fibrillation, plasma flecainide level before terminal ventricular fibrillation (VF) was not toxic, but prolongation of CT in the 5 dogs was remarkable (30 +/- 9%). Thus, VF resistant to defibrillation is not necessarily associated with both toxic plasma drug level and remarkably decreased conduction. Reliability of these valuables as indicators of fatally deteriorated defibrillation efficiency may vary among antiarrhythmic agents.

Twenty one patients with resectable oral cancer received two courses of induction chemotherapy with peplomycin (PEP), vincristine (VCR), mitomycin C (MMC) and cisplatin (CDDP). Five patients had a complete response to the therapy and 9 had a partial response. Histological evaluation by Ohboshi-Shimozato classification indicated that Grade IV was obtained in 7 cases, Grade III was in 4 cases. Moreover, the study suggested that this regimen was less effective for metastatic lymph lesions than that for the primary tumors.

To characterize 201Tl uptake in patients with bone and soft-tissue tumor, we studied 49 patients with surgically proven tumors and one patient with a tumor diagnosed arteriographically. In 37 of our 50 patients, the tumor was evaluated with 201Tl and arteriography. Moreover, in 14 of patients with pre-operative chemotherapy, pathologic changes were graded on the basis of percent tumor necrosis as defined histologically. The percent tumor necrosis histologically was compared with changes in the scintigraphic and conventional angiographic studies. Radiologic comparisons demonstrated a high degree of correlation with images of 201Tl and both arterial and blood pool phase of 99mTc-HMDP. Ninety-six percent of 28 malignant tumors had positive 201Tl uptake. None of the patients showed any thallium accumulation in the soft tissues or skeleton adjacent to the lesion. Activity of 201Tl was mainly dependent upon a tumor blood flow and a vascular density. In of 14 cases with the preoperative chemotherapeutic treatment, 201Tl scintigraphic changes showed concordance with % tumor necrosis. Thallium-201 was superior to 99mTc-HMDP in predicting tumor response to chemotherapy. Interestingly, delayed images of 99mTc-HMDP of 5 responders with90% tumor necrosis showed decreased uptake in the adjacent bone to the tumor mass lesions. It seems to be quite all right to consider that a major determinant of 201Tl uptake is intratumoral angiogenecity, which is closely connected with tumor viability. Therefore, 201Tl is a sensitive radiopharmaceutical for detection of vascular rich bone and soft-tissue tumors, and appears to be a simple and an accurate test for evaluating the response to specific therapeutic regimens of malignant bone and soft-tissue tumors.

The presence of superoxide generated by polymorphonuclear leukocytes (PMNs) was demonstrated in an experimental autoimmune uveoretinitis (EAU) model. Histopathological examination of the eyes, enucleated sequentially after the onset of EAU, and determination of retinal lipid peroxidation (LPO) revealed an increase in LPO products with progressive retinal tissue damage. In addition, histopathological changes, predominantly degeneration of the retinal outer segments, and increased retinal LPO were confirmed in vitro by culturing naive neural retina with activated PMNs. This increased LPO was inhibited by superoxide dismutase (SOD). These data suggest that lipid peroxidation reaction involving superoxide may play an important role in the pathogenesis of retinal tissue damage in ocular inflammatory disease characterized by the infiltration of PMNs.

S-antigen or interphotoreceptor retinoid-binding protein (IRBP), when injected with Freund's complete adjuvant into mice, does not easily cause experimental autoimmune uveoretinitis (EAU). In this report, we describe the results of injecting IRBP with Freund's complete adjuvant, together with the intraperitoneal administration of Bordetella pertussis, into several types of congenic mice (B10, B10A, B10BR, B10D2). These congenic mice, of C57BL/10 (B10) origin, differ at the H-2 locus on chromosome 17. We were able to produce EAU in 38.5% of B10A mice, and 12.5% of B10BR mice, confirming that EAU can develop in these mice that carry the k genotype at the K, I-A, and I-E regions of the major histocompatibility complex (MHC) H-2 locus. We believe that the k genotype of the K, I-A, and I-E regions is important as a factor in the pathogenesis of EAU in congenic B10 mice.

The nucleotide sequence of the Escherichia coli pgsA gene, encoding phosphatidylglycerophosphate synthase, is revised to code for an enzyme of 182 amino acid residues, instead of the 216 of a previous work (A. S. Gopalakrishnan, Y.-C. Chen, M. Temkin, and W. Dowhan, J. Biol. Chem. 261:1329-1338, 1986). The revised structure now explains the properties of the enzyme. Three pgsA mutants of different phenotypes were also analyzed: pgsA3, pgsA36, and pgsA10 have single-base replacements in codons 60 (Thr-->Pro), 1 (ATG-->ATA), and 92 (Thr-->Ile), respectively.

Enzyme-linked immunosorbent assays (ELISA) were developed to specifically quantify the two major allergens from Japanese cedar pollen, Cry j I and Cry j II. Polystyrene microplates coated with antibodies specific for Cry j I or Cry j II were incubated with an allergen and then with biotinylated anti-Cry j I or Cry j II antibody. The bound allergen-biotin Ab complexes were detected with HRPO-conjugated streptavidin and an enzyme substrate. The working ranges of Cry j I ELISA and Cry j II ELISA were 0.3-20 ng/ml and 0.6-20 ng/ml, respectively. Intra- and inter-assay coefficients of variation for reproducibility were 1.5-10.3% and 0.9-12.9%. These ELISA systems showed no cross-reactivity between Cry j I and Cry j II and showed little cross-reactivity with pollen allergens of plants botanically related to the Japanese cedar. Using the Cry j I ELISA and the Cry j II ELISA, it was possible to quantify Cry j I and Cry j II easily and accurately. These ELISA systems will be useful in various fields, especially for the analysis and standardization of the allergens necessary for diagnosis and treatment of Japanese cedar pollinosis.

Autoimmune uveoretinitis and pinealitis have been shown to develop spontaneously in BALB/c nude mice after their T cell function has been reconstituted by embryonic F344 rat thymus grafting (TG nude mice). Because anti-IRBP antibodies were detected in these mice, it was concluded that IRBP was the target antigen. In this study, we removed the eyes and/or the pineal body from TG nude mice, and examined anti-IRBP antibodies in their sera. It appeared that IRBP originating from the eyes and the pineal body were the immunogenic antigens in the TG nude mice, but the IRBP from the eyes was found to be more immunogenic and pathogenic than that from the pineal body. We also found that the incidence of uveoretinitis increases with pinealectomy in TG nude mice, even though the immune system is not affected.

Retinoids, in particular retinoic acid, are required for the normal growth and maintenance of many types of cells, including epithelial cells. The metabolism of lens epithelial cells, which are exposed to aqueous humor in the anterior chamber, is thought to be dependent upon aqueous humor dynamics. In human eyes undergoing cataract surgery, we measured retinoic acid levels using reverse-phase high performance liquid chromatography to investigate the possible role of aqueous humor in the transport of retinoic acid to lens epithelial cells. The retinoic acid level in the aqueous humor and the lens epithelial cells was 23.3 +/- 2.3 pmol/ml and 1.8 +/- 0.8 pmol/micrograms protein, respectively. Fluorescence spectra study suggested the presence of endogenous retinoid-protein complexes in the aqueous humor. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis showed that the major protein in aqueous humor was albumin, a natural carrier protein of retinoic acid in the blood. From these results, we conclude that the aqueous humor may supply retinoic acid to the lens epithelial cells in human eyes.

Among 330 vibration-exposed workers, 24 cases of hypothenar hammer syndrome in 29 hands were diagnosed by arteriography. The right hand was involved in 13, the left hand in six, and both hands in five cases. The mean age was 55 years, mean duration of vibration exposure 19.4 years, and mean duration of episodic Raynaud’s phenomenon 6.4 years. The vascular lesions of the ulnar arteries were classified into three major types with subtypes. Type 1: stenosis of the superficial palmar arch around the hook of the hamate. Type 2a: occlusion of the superficial palmar arch around the hook of the hamate. Type 2b: occlusion of both superficial and deep palmar arches around the hook of the hamate. Type 3a: occlusion of the ulnar artery at the proximal part of the wrist. Type 3b: occlusion of the ulnar artery near the wrist with the occlusion of the dorsal carpal branch of the ulnar artery.

We performed local resection of a ciliary body tumor, which was diagnosed as pleomorphic adenocarcinoma arising from nonpigmented epithelium of the ciliary body. The patient was a 57-year-old male, and the tumor was found incidentally at an ophthalmologic examination. Since the possibility of malignant tumor could not be ruled out, local resection of the tumor was performed. The tumor developed from the pars plicata and the size was 5.5 x 6.0 x 7.5 mm. Histologically, the tumor cells displayed heteromorphism and revealed tubular and glandular structures which continued to the ciliary body epithelium. Melanin pigment was not observed, except in one small area of the tumor. The interstitium of the tumor tissue was stained with alcian blue, and a immunohistochemical study showed that tumor cells were positive for epithelial membrane antigen (EMA) and vimentin, but negative for S-100 protein and carcinoembryonic antigen (CEA). Electron microscopy revealed desmosomes between cells, and microvilli were observed at the margin of the glandular cavity structure. In this case, no severe complications occurred even after local resection and good visual function was maintained.

Cry j II, the second major allergen of Japanese cedar (sugi, Cryptomeria japonica) pollen was examined for the allergenicity by intradermal test and RAST. Nineteen of the 25 allergic patients examined, showed positive reaction to the Cry j II. Contents of Cry j II in the extracts of the pollen collected in various regions from 1977 to 1991 showed yearly variation ranging from 2.9 to 14 mg/100 g pollen, whereas the amount of Cry j I in the extract was comparatively stable at about 35 mg/100 g pollen. Physicochemical treatments of Cry j I and Cry j II suggested that specific human IgE antibodies and some mAbs bind to conformational epitopes which are denatured and destroyed by certain treatments.

The patient was a 42-year-old man. When he was a third grade pupil of elementary school, he was diagnosed as having miliary tuberculosis. He was absent from school for 2 years for the treatment of the disease. However, miliary tuberculosis did not improve in spite of 2 years of treatment. At that time he was diagnosed as having pulmonary alveolar microlithiasis. He did not receive any treatment for the following 30 years. Recently, he visited our department because of occasional chest pain. The following tests were performed; chest CT, tomography, respiratory function test, RI test (99mTc bone scintigram and 67Ga scintigram) and bronchoscopy. Bronchoalveolar lavage (BAL) was performed of B5b, and transbronchial lung biopsy (TBLB) of left B5b, B8b, B9b and B10b to make the accurate diagnosis of pulmonary alveolar microlithiasis. This case of pulmonary alveolar microlithiasis with a protracted course of 30 years (in which chest X-ray films taken 27 years ago were available) is reported together with a discussion of the literature.

Forty sea from French patients allergic to Cupressus sempervirens pollen were tested for cross-reactivities against Cry j I, Cry j II (major allergens of Cryptomeria japonica pollen) and other pollen allergens from botanically related plants. Seventy-three per cent of the sera reacted with either Cry j I or Cry j II, or with both of them. These IgE cross-reactions were blocked effectively by mAb 046 (anti-Cry j I) or N26, T27 (anti-Cry j II), and weakly by mAbs 052, 027 and 026 (anti-Cry j I). Furthermore, the IgE antibodies in two sera, #40 and #11, bound to peptide fractions obtained from enzyme-digested Cry j I, and mAb 027 could also bind to the fractions. Analyses of the amino acid sequences of the peptides revealed that reactive peptides contained "NGNATPQLTKNAGVLTCSLSKR" sequence and the third residue N3 was glycosylated, however, when the N3 was not glycosylated, the IgE antibodies did not react, but mAb 027 could. The glycosylation of the N3 might be required for IgE-binding to the peptides. Sugar component on the N3 residue was found to be 0.4 mol galactose, 1.3 mol mannose, 0.8 mol fucose and 2.0 mol N-acetyl-glucosamine. Cross-reactivities against other pollen allergens from botanically related plants were found in most of the sera. However, many of these reactivities were detected by sandwich ELISA but not by an ELISA using allergen-coated plates, indicating that it is important to select an appropriate ELISA procedure in order to detect an allergen or an IgE antibody to an allergen.

In order to analyze the onset mechanism of experimental autoimmune uveoretinitis (EAU), two experimental models were used; one was EAU induced by one injection of purified bovine interphotoreceptor retinoid-binding protein (IRBP) with complete Freund's adjuvant in Lewis rat, and the other was an IRBP-induced autoimmune uveoretinitis that occurred spontaneously in nude (nu/nu) mice at 4 weeks of age reconstituted by the grafting of rat embryonic thymus (TG nude mouse). EAU develops when the IRBP-reactive lymphocytes in the regional lymph-nodes are activated. Activation begins when the T lymphocyte recognizes the peptide for the epitope bound to a major histocompatibility complex (MHC) molecule in the antigen-presenting cell by way of the T-cell receptor (TCR). In EAU, ten peptide residues p1182-1191 of the IRBP amino acid sequence, were revealed to be sufficiently capable of lymphocyte activation for EAU, and it was also shown that amino acid positions 1182W (tryptophane), 1185G (glycine), 1186V (valine) and 1188P (proline) of IRBP play important roles as the epitopes or agretopes in developing EAU. On the other hand, two amino acids of IRBP, amino acid positions 1182W (tryptophane) and 1194P (proline) were shown to be the agretopes inducing autoimmune uveoretinitis in the TG nude mouse. A study of the variable region of the TCR with a residual p1182-1194 specific T-cell line from the TG nude mouse revealed that as many as 96% utilized the T-cell receptor V beta 6 gene and that the peptide-MHC molecule complex was recognized by restricted receptors. Adhesion molecules such as ICAM-1 and LFA-1 were also found to play an important role as cofactors in activation of lymphocytes in the antigen-recognition process of EAU. Uveoretinitis seemed to result from an immune reaction in the eye occurring when the T lymphocyte arrives there, activating the immunological process. ICAM-1 and LFA-1 were also found to be involved in the infiltration process of inflammatory cells: our immunohistological examination revealed that ICAM-1 was present in the retinal pigment epithelium and epithelium of the ciliary body composing the blood-ocular barrier. In contrast, LFA-1 was expressed in the infiltrating cells. Finally, the tolerance of IRBP was discussed and it was experimentally demonstrated that the absence of IRBP-induced uveoretinitis in human beings and certain experimental animals resulted from endogenous IRBP serving as a tolerogen; we assumed that the breakdown of this self-tolerance would induce EAU due to thymic dysfunction or IRBP antigen injection.

The 4 anti-Cry j I mAbs showing an epitope specificity different from each other, 046, 029, 026 and 027, were selected to analyze the structure of the antigenic determinant for each mAb on a Cry j I molecule. Immunoreactive fragments in enzyme-cleaved Cry j I were detected by means of the adsorption on the mAb column and of the binding to the mAbs on Elisa. The mAb 026 was found to be reactive to the fragments containing a Cry j I N-terminal region obtained by V8 protease or pepsin digestion, but not to those by lysylendopeptidase digestion. The mAb 027 was found to be capable of binding to the fragments containing a linear structure of Asn-Ala-Gly-Val-Leu-Thr-Cys-Ser-Leu-Ser-Lys, which were generated by V8 protease, lysylendopeptidase or pepsin digestion. Furthermore, the synthetic peptide Asn-Ala-Gly-Val-Leu-Thr-Cys-Ser- Leu-Ser-Lys-Arg could bind to 027, but not to 026, and could inhibit the binding of 027 to Cry j I or to its immunoreactive fragments. No fragments capable of reacting to the mAbs 046 and 029 could be found in this study, suggesting that 046 and 029 recognize a conformationally constituted epitope of Cry j I molecule which is destroyed by enzymatic cleavage. The epitope recognized by the mAbs 027 or 026 was found to be located in conformationally hidden parts of the molecule which was exposed to react to the mAbs only after the physicochemical or enzymatic treatment.