Oxidative Stress Inhibits Endotoxin Tolerance and May Affect Periodontitis.

Periodontal disease is caused by dysbiosis of the dental biofilm and the host inflammatory response. Various pathogenic factors, such as proteases and lipopolysaccharides (LPSs) produced by bacteria, are involved in disease progression. Endotoxin tolerance is a function of myeloid cells, which sustain inflammation and promote tissue regeneration upon prolonged stimulation by endotoxins such as LPS. The role of endotoxin tolerance is gaining attention in various chronic inflammatory diseases, but its role in periodontal disease remains elusive. Oxidative stress, one of the major risk factors for periodontal disease, promotes disease progression through various mechanisms, of which only some are known. The effect of oxidative stress on endotoxin tolerance has not yet been studied, and we postulated that endotoxin tolerance regulation may be an additional mechanism through which oxidative stress influences periodontal disease. This study aimed to reveal the effect of oxidative stress on endotoxin tolerance and that of endotoxin tolerance on periodontitis progression. The effect of oxidative stress on endotoxin tolerance was analyzed in vitro using peritoneal macrophages of mice and hydrogen peroxide (H2O2). The results showed that oxidative stress inhibits endotoxin tolerance induced by Porphyromonas gingivalis LPS in macrophages, at least partially, by downregulating LPS-elicited negative regulators of Toll-like receptor (TLR) signaling. A novel oxidative stress mouse model was established using SMP30KO mice incapable of ascorbate biosynthesis. Using this model, we revealed that oxidative stress impairs endotoxin tolerance potential in macrophages in vivo. Furthermore, gingival expression of endotoxin tolerance-related genes and TLR signaling negative regulators was decreased, and symptoms of ligature-induced periodontitis were aggravated in the oxidative stress mouse model. Our findings suggest that oxidative stress may contribute to periodontitis progression through endotoxin tolerance inhibition.

Correlation of c-myc expression with nuclear pleomorphism in human renal cell carcinoma.

The expression of the c-myc gene product in renal cell carcinomas was examined by immunostaining with monoclonal antibody (mAb) MYC-1. The effects of preservation and fixation of tissues on staining were first examined. In cryostat sections fixed with 4% buffered formalin for 15 min, staining was observed in the nucleus. On the other hand, in paraffin sections after fixation with 10% formalin, staining was observed in the cytoplasm, but not in the nucleus. Because c-myc protein has been shown to be a nuclear protein, the finding that c-myc protein was not detectable in the nucleus appeared to be due to the preservation or fixation procedures used. Therefore, cryostat sections fixed with 4% formalin were used to investigate the correlation between the reaction of MYC-1 mAb and nuclear pleomorphism in primary and metastatic renal cell carcinomas. Among 41 primary tumors, positive staining was observed in 2 of 17 tumors (12%) of grade 1, 17 of 21 (81%) of grade 2, and all 3 (100%) of grade 3. Among 17 metastatic tumors, positive staining was not observed in any of the 5 (0%) of grade 1 but was observed in 2 of 4 (50%) of grade 2 and all 8 (100%) of grade 3. Thus, the frequency of the positive reaction with MYC-1 mAb was correlated with nuclear pleomorphism in primary and metastatic renal cell carcinomas. The reaction of Ki-67 mAb, which recognized a nuclear antigen present in proliferating cells, was also correlated with nuclear pleomorphism. These findings suggest that the c-myc gene product plays a role in cell proliferation in renal cell carcinomas.

A case of familial amyloid polyneuropathy homozygous for the transthyretin Val30Met gene with motor-dominant sensorimotor polyneuropathy and unusual sural nerve pathological findings.

OBJECTIVE: To report a case of familial amyloid polyneuropathy homozygous for the amyloidogenic transthyretin (ATTR) Val30Met gene with motor-dominant sensorimotor polyneuropathy and unusual sural nerve pathological findings. METHODS: Mass spectrometry analysis and polymerase chain reaction-restricting fragment length polymorphism were performed. A right sural nerve biopsy specimen was obtained for histological investigation. SETTING: Academic medical center. RESULTS: A 56-year-old Japanese man living in a local town (Nakajima, Japan) in Ishikawa Prefecture, a nonendemic area of type I familial amyloidotic polyneuropathy, had vitreous amyloidosis, motor-dominant sensorimotor polyneuropathy, erectile dysfunction, and urinary incontinence. He had neither orthostatic hypotension nor indolent diarrhea. Restriction enzyme analysis with EcoT22 I of amplified DNA and mass spectrometry analysis revealed homozygosity for ATTR Val30Met. Of 8 family members, 5 were evaluated and found to be heterozygous for ATTR Val30Met; a family history found no relative with the similar neurologic disorders. The sural nerve biopsy specimen showed focal edema and an amyloid deposit in the subperineural tissue, associated with moderate loss of myelinated and unmyelinated fibers. CONCLUSIONS: In addition to the findings characteristic of homozygosity for ATTR Val30Met such as vitreous amyloidosis and relatively less autonomic involvements, this case had the unique findings of motor-dominant sensorimotor polyneuropathy and unusual sural nerve biopsy specimen results.

Pulmonary vascular involvement in sarcoidosis: a report of 40 autopsy cases.

We examined pulmonary vascular involvement in 40 autopsy cases of sarcoidosis. In these cases granulomatous involvement was observed at all levels from large elastic pulmonary arteries to venules, and venous involvement was more prominent than arterial involvement. The extent of granulomatous vascular involvement was related to that of parenchymal granuloma. No significant difference was found between upper and lower lobes in the incidence of granulomatous vascular involvement. The distribution of granulomata in the blood vessels was segmental and adventitial, and medial involvement was prominent in the larger vessels. Healed lesions of granulomatous vascular involvement also were observed at various levels in blood vessels. Prominent granulomatous involvement was found in the lymphatic capillaries and collecting lymphatic vessels in lungs with sarcoidosis. Serial sections of the lungs demonstrated interstitial granuloma directly connecting the lymphatic capillaries around small blood vessels. Granulomatous involvement in vasa vasorum and lymphatic capillaries is likely to be an important factor in the pathogenesis of granulomatous vascular involvement in lungs with sarcoidosis. The present study suggests that granulomatous vascular involvement and its sequelae may contribute to the development of pulmonary sarcoidosis.

The lung in polyarteritis nodosa: a pathologic study of 10 cases.

Polyarteritis nodosa (PAN) is characterized by necrotizing arteritis of medium-sized and small arteries in various organs. Pulmonary artery involvement in PAN has been considered rare. Previously, it also has been thought that patients with PAN do not have interstitial pneumonitis and fibrosis. A detailed pathologic analysis of pulmonary diseases associated with PAN was made in 10 autopsy cases of PAN. Arteritis affecting bronchial arteries was present in seven patients (70%). The data obtained suggest that arteritis in the lung in patients with PAN is more common than has been recognized previously. Diffuse alveolar damage (DAD) involving all lobes bilaterally was present in five patients; it was acute in two patients and organizing in three. In the patients with organizing DAD the degree of fibrosis in the interstitium differed among the lobes, and the fibrosis was more severe in the lower lobe than in the other lobes. Two patients presented with interstitial fibrosis with honeycomb lung of the posterior and lateral basal segments of the lower lobes of both lungs; in one of these patients interstitial fibrosis was present in an area of organizing DAD. Five patients died of respiratory failure resulting from DAD. In conclusion, it is important to consider DAD and interstitial fibrosis as complications of PAN.

Advantage of preoperative portal vein occlusion for hepatectomy that exceeds portal vein occluded lobes.

BACKGROUND: The purpose of our study was to examine the effect of preoperative portal vein (PV) occlusion on hepatic reserve function after extended hepatectomy that is an excision of areas beyond the PV occluded lobes. METHODS: Male Wistar rats were divided into three groups and underwent a two-stage operation: a PVL-hepatectomy group (ligation of the PV [PVL] of the left and median lobes followed by hepatectomy of the right lobes together with the PV occluded lobes), a sham-88% hepatectomy group (sham operation without PVL followed by hepatectomy corresponding to the lobes excised in the PVL-hepatectomy group), and a sham-67% hepatectomy group (sham operation followed by hepatectomy of the left and median lobes to approximate the volume excised in the PVL-hepatectomy group). In all subjects, hepatectomy was carried out 7 days after the PVL or sham operation. On days 0, 1, 2, and 3 after hepatectomy, liver weight, histologic elements, DNA synthesis rates, energy charge, adenine nucleotides, and lipoperoxide levels of the remaining liver were determined. RESULTS: In the sham-88% hepatectomy group, the volume of resected liver was 88.2% +/- 0.5%. In the PVL-hepatectomy group it was 69.1% +/- 0.8%, although anatomically identical lobes were excised. At the time of hepatectomy, DNA synthesis, hepatic concentrations of adenine nucleotides and lipoperoxide, and serum liver function tests showed similar results in all three groups. The survival rate 3 days after hepatectomy was significantly low (53%) in the sham-88% hepatectomy group, whereas it was 100% in the PVL-hepatectomy and sham-67% hepatectomy groups. The gain in liver weight per day was significantly lower in the sham-88% hepatectomy group than in the other two groups. The decline in hepatic energy charge after hepatectomy was less, with less activated DNA synthesis, in the PVL-hepatectomy group compared with the sham-88% hepatectomy and sham-67% hepatectomy groups. Lipoperoxide concentration in the PVL-hepatectomy group was significantly lower than that in the sham-88% hepatectomy and sham-67% hepatectomy groups. CONCLUSIONS: Preoperative PV occlusion not only increases the remaining liver volume but also is advantageous to hepatic reserve after hepatectomy that exceeds PV occluded lobes.

Blood supply of the parathyroid gland from the superior thyroid artery.

BACKGROUND: There is considerable controversy about the arterial supply to the superior parathyroid glands. Knowledge of this blood supply should be important for the surgeon performing thyroid and parathyroid operations. The purpose of this investigation was to document whether the superior parathyroid glands receive their blood supply from the superior thyroid artery. METHODS: We injected contrast material into the superior thyroid artery in 52 cadavers and determined the arterial blood supply to the parathyroid glands by using a dissecting microscope. RESULTS: The upper parathyroid gland was identified in 51 instances and the upper and lower glands in 26 instances on the side of injection. Of 92 parathyroid glands identified, 57 glands (62%) had a single artery, 26 (28%) had two, and 9 (10%) had three or more arteries. In 9 (45%) of the 20 cases specifically examined, a distinct anastomosing branch was identified between the inferior and the superior thyroid arteries, from which the upper parathyroid artery arose. CONCLUSIONS: Our study documented that the superior thyroid artery almost always supplies the upper parathyroid glands. Forty-five percent of the subjects had a distinct anastomosing branch between the superior and inferior thyroid arteries, which should be kept intact at operation to preserve the upper parathyroid function. One third of the parathyroid glands have two or more parathyroid arteries.

Changes in serum hypoxanthine levels by exercise in obese subjects.

To study on effect of obesity on changes in serum hypoxanthine with exercise, exercise stress testing with treadmill was performed on 7 obese subjects (body mass index [BMI], 30.6 +/- 3.2 kg/m(2)) and 16 healthy volunteers (BMI, 21.5 +/- 2.10 kg/m(2)). Expiratory gas analysis during exercise showed that peak Vo(2) was significantly lower in the obese group than in the control group (28.1 +/- 4.0 v 37.1 +/- 4.7 mL/kg/min; P <.001). Furthermore, the obese group had lower anaerobic threshold (AT) values (P <.005), respiratory quotient at AT (P =.003), and exercise capacity reserve (P =.002) than the control group. Baseline serum hypoxanthine levels were significantly higher in the obese group than in the control group (3.46 +/- 3.70 v 1.23 +/- 1.16 micromol/L; P <.05). Exercise induced a pronounced increase in serum hypoxanthine level in the obese group compared with the control group (10.65 +/- 6.81 v 43.86 +/- 4.56 micromol/L; P <.01). Serum levels of uric acid before and after load were also higher in the obese group than in the control group (404 +/- 43 v 302 +/- 77 micromol/L; P <.005). A pronounced increase in hypoxanthine with exercise may result in organ damage caused by free radicals, and intermittent training from mild intensity may be less hazardous for exercise treatment of obesity.

Postoperative systemic adjuvant chemotherapy for bladder cancer.

Forty-six patients with bladder cancer without distant metastasis (M0) were treated by chemotherapy as an adjuvant after total cystectomy using three protocols (protocol I: adriamycin 50 mg/m2, cyclophosphamide 500 mg/m2, and cis-platinum 50 mg/m2 i.v., starting at least 2 weeks after surgery every 3 weeks for three cycles; protocol II: adriamycin 30 mg/m2 on the 1st postoperative day, cyclophosphamide 300 mg/m2 on the 1st and the 7th days; protocol III: FT-207 60 mg/m2, p.o. every day for 1 year). Average follow-up periods after surgery by protocol were 18 months for protocol I, 31 for protocol II, and 43 for protocol III. Analysis of the survival curves showed no statistically significant differences among the three groups or between a historical control group of 106 patients and the entire patient population examined in the present study. The histopathological grades recorded in the 46 patients were G1, G2, and G3 in 1, 22, and 23, respectively. However, from a study of 48 pT3 and pT4 cases, the survival rate of 10 patients receiving protocol I therapy was statistically significantly higher than those of 12 patients treated according to protocol II and of 26 historical controls, at 1 year and 2 years, respectively. Toxic effects, with gastrointestinal symptoms including nausea and vomiting and myelosuppression (including leukopenia and anemia) were more frequent with protocol I. Alopecia occurred in about 80%-90% of patients treated according to either protocol I or II. Almost all patients could tolerate adjuvant chemotherapy, and none of them died as a result of these regimens. The results recorded in this study justify the evaluation of combination adjuvant chemotherapy with adriamycin, cyclophosphamide and cis-platinum in a prospectively randomized trial.

Adjuvant and neoadjuvant chemotherapy for invasive bladder cancer.

A total of 20 patients with primary invasive bladder cancer who underwent radical cystectomy received postoperative adjuvant chemotherapy using a CAP (cyclophosphamide, doxorubicin, and cisplatin) or modified M-VAC (methotrexate, vinblastine, pirarubicin, and cisplatin) regimen. In all, 16 of the patients were treated with CAP and 4 received the modified M-VAC regimen. Of the 20 patients, 17 had transitional-cell carcinoma with or without non-transitional-cell elements. All of the patients had tumors with a histological grade of G2 (6 cases) or G3 (14 cases). As for lymph-node metastasis, there were ten N0 cases, three N1 cases, six N2 cases, and one N3 case. Adjuvant chemotherapy was usually commenced 2 weeks after the surgery and was given every 3-4 weeks for two or three cycles. The 5-year survival rate of these 20 patients was 65.9%, whereas that of 49 patients who did not receive any adjuvant chemotherapy was 30.2%. Regarding toxicity, both of the adjuvant chemotherapy regimens used in this study were generally well tolerated. The most common toxic effects were gastrointestinal symptoms, alopecia, and myelosuppression. Another 19 patients with invasive transitional-cell carcinoma of the bladder received 2 or 3 cycles of neoadjuvant chemotherapy using the modified M-VAC or MEC (methotrexate, epirubicin, and cisplatin) regimen. Of 18 pathologically evaluable patients who underwent radical cystectomy or partial cystectomy, the stage was pT0 in 3 cases (17%), pTis in 3 (17%), pT1 in 3 (17%), and pT2 or higher in 9 (50%). The 4-year survival rate of 18 patients who received neoadjuvant chemotherapy was 71.5%. Regarding toxicity, one patient died of a bowel complication after surgery, and the complication was suggested to be drug-induced.

Non-N-methyl-D-aspartate glutamate receptors mediate oxygen--glucose deprivation-induced oligodendroglial injury.

Cells of oligodendroglial lineage are susceptible to oxygen and glucose deprivation. When oligodendrocyte-like cells differentiated from CG-4-immortalized rat O-2A progenitor cells were exposed to hypoxia alone or glucose deprivation alone for 48 h, release of lactate dehydrogenase (LDH) into the culture medium did not increase. However, when cells were deprived of both oxygen and glucose for 6 or 12 h preceding reoxygenation for 2 h, LDH release increased. Adding glucose to the medium protected against cell death and increased lactate production in a concentration-dependent manner. Cell damage induced by deprivation of oxygen and glucose was prevented by calcium-free medium or by non-N-methyl-D-aspartate glutamate receptor (GluR) antagonists, such as 6-cyano-7-nitroquinoxaline-2,3-dione or LY293558, but not by the voltage-dependent calcium channel blocker, nimodipine, or by the N-methyl-D-aspartate GluR antagonist, MK-801. The glutamate concentration in the medium from cells exposed to oxygen-glucose deprivation for 12 h was 49.70+/-3.04 microM/l, which is sufficient to activate GluRs during deprivation of oxygen and glucose. Apoptotic cells detected by terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick end-labeling (TUNEL) or Hoechst 33258 staining did not increase in cells exposed to oxygen-glucose deprivation for 12 h and subsequent reoxygenation for 2 h. No DNA laddering was detected by agarose gel electrophoresis from cells exposed to deprivation of oxygen and glucose. Neither acetyl-YVAD-CHO, an inhibitor of caspase-1-like proteases, nor acetyl-DEVD-CHO, an inhibitor of caspase-3-like proteases, prevented oxygen-glucose deprivation-induced injury. Thus, oxygen and glucose deprivation causes calcium-influx-induced necrotic cell damage in cells of oligodendroglial lineage via non-N-methyl-D-aspartate GluR channels.

A multivariate analysis of prognostic factors related to recurrence and progression of superficial bladder cancer.

Prognostic factors related to the recurrence and progression of superficial primary bladder cancers were analyzed by Cox's proportional hazards regression model. We followed 75 patients (stage Ta, 49 cases; T1, 26 cases; grade G1, 42 cases; G2, 29 cases; G3, 4 cases) after transurethral resection for 10 to 74 months (median 38 months). The antibodies reactive with the products of oncogenes [anti-c-myc oncoprotein (MYC-1); anti-c-erbB-2 oncoprotein], tumor suppressor gene [anti-p53 mutant protein (BP53-12)], growth factor receptor [anti-transferrin receptor (HBT-2)], proliferation [anti-proliferatioe nuclear antigen (Ki-67)], and malignant transformation (B1.4) were used for immunohistochemical staining. The reactivities of mAb B1.4, HBT2, and BP53-12 were significantly increased according to the grade, and those of mAb Ki-67, MYC-1, and c-erbB-2 were not. The reactivities of all antibodies were not significantly different between stages Ta and T1. As prognostic factors, stage, grade, tumor number, urinary cytology, and reactivities of the above six antibodies were used for the analysis. Urinary cytology, multifocality, and the reactivity of mAb Ki-67 showed a relative but significant high risk for recurrence, and the reactivities of mAb HBT2, mAb B1.4, and mAb Ki-67 showed a significant high risk for progression in the multivariate analysis. These results suggest that mAb B1.4 may be useful as a new prognostic factor for the progression of superficial bladder cancer.

Expression of Fas and Fas ligand in the testes and testicular germ cell tumors: an immunohistochemical study.

The Fas-Fas ligand system plays a crucial role in the production of a signal for apoptosis in the immune system. In the present study, expression of Fas and Fas ligand in the testes and testicular germ cell tumors was examined immunohistochemically. Expression of both Fas and Fas ligand was found on Leydig cells, Sertoli cells, and germ cells in the testis, and on epithelial cells in the epidydimal duct. Expression of both Fas and Fas ligand was also found in all 23 seminomas, 8 embryonal carcinomas, and 3 yolk sac tumors which were examined in this study. Western blot analysis after sodium dodecyl sulfate (SDS) polyacrylamide gel electrophoresis under a reducing condition with tissues of the thymus, the testis, and a seminoma showed a single major band bound to the antibody for Fas or Fas ligand at the position of molecular weight slightly more than 47.5 kilodalton. Since both Fas and Fas ligand are expressed on normal testicular cells, and on cells of testicular germ cell tumors, the Fas-Fas ligand system in these cells seems to play a role other than producing a signal for apoptosis.

Amyotrophic lateral sclerosis associated with sarcoidosis.

We report a rare association of amyotrophic lateral sclerosis (ALS) with incidental pulmonary and muscle sarcoidosis. A 63-year-old woman presented with slowly progressive weakness and atrophy of the extremities starting from the left leg. The biopsy of a small mass in the left gastrocnemius revealed a typical sarcoid nodule. She was treated with corticosteroid for possible sarcoid neuromyopathy. In spite of the treatment, her clinical course was relentlessly progressive and she died of bulbar palsy. Autopsy revealed a loss of motor neurons in the anterior horn, vacuolar degeneration of the lateral funiculus, and noncaseating granulomas in paratracheal lymph nodes and lungs. No granulomatous lesion or cellular infiltration was found in the spinal cord.

Carcinoma of the extrahepatic bile duct: mode of spread and its prognostic implications.

BACKGROUND/AIMS: The postoperative course of patients with bile duct carcinoma after surgical resection remains dismal. The purpose of this study was to examine the mode of spread from the original site of the carcinoma and its prognostic significance. METHODOLOGY: A total of 46 Japanese patients with extrahepatic bile duct carcinoma who underwent surgical resection from January 1976 to August 1995 were retrospectively reviewed. RESULTS: Out of 24 patients with upper bile duct carcinoma, 16 (67%) were papillary or well differentiated tubular adenocarcinoma of the polypoid or nodular type on gross configuration, whereas 7 of 11 patients (64%) with lower bile duct carcinoma had moderately differentiated tubular adenocarcinoma or poorly differentiated adenocarcinoma of the annular constrictive or diffusely infiltrating type (p < 0.01). A noteworthy feature was perineural invasion (18/24, 75%) in the former group. Lymphatic permeation and venous invasion were seen in 50% and 38% of the former group and these were present in 73%, and in 73% of the latter (p < 0.01). Lymph node metastasis was most frequent in patients with lower bile duct carcinoma (5/11, 45%). Periductal spread along the bile duct toward the liver was more frequent and extensive in the infiltrating type than in the polypoid, nodular, or annular constrictive type. Carcinoma of the polypoid type often extended along the mucosa and rarely through the periductal layer. The mean distance between the edge of carcinoma invasion estimated by cholangiography and that proved by histology on the resected specimens was 6.1 +/- 6.1 mm in the hepatic and 6.2 +/- 9.1 mm in the duodenal direction. In all 11 patients with lower bile duct carcinoma, surgical margins were free of cancer cells, while they were affected by malignant cells in 17 of 24 patients with upper bile duct carcinoma. Univariate log-rank analysis showed that venous invasion, perineural infiltration, and the presence or absence of cancer cells at the cut edge of the bile duct in the hepatic direction and at the resection margins in the transverse direction were significant prognostic factors. Multivariate Cox regression analysis revealed that cancer cells at the edge of the bile duct in the hepatic direction constitute a significant and independent prognostic variant. CONCLUSIONS: Extrahepatic bile duct carcinoma should be excised to a distance of 1.5 cm from the edge of the carcinoma as estimated on cholangiography to achieve cancer-free margins, especially at the resected margins in the hepatic direction.

Venous pressure and compliance of the peripheral capacitance vessels.

Compliances of the peripheral capacitance vessels decreased gradually in accordance with the increase in pressure of the brachial vein. The relationship between them formed a number of hyperbolic-like curves, the same results as those found in many cases of both normal subjects and patients with congestive heart failure. The decrease of compliance of the peripheral capacitance vessels was not the result of an organic change, but of a functional change of the vessels caused by distention.

Clinical studies on peripheral hemodynamics in arterial hypertension.

Digital blood pressure and flow were measured in both normal subjects and patients with essential hypertension by means of the apparatus which have been recently devised, and peripheral vascular resistance was calculated according to Poiseuille's law in order to compare them. 1. Digital blood pressure is higher, the digital blood flow is less and the peripheral vascular resistance is stronger in patients with essential hypertension than in normotensives. 2. Hypertensive patients with ischemic heart disease, calcification of the aortic arch, left ventricular hypertrophy and heart size greater than 53% of the cardio-thoracic ratio were higher in the digital pressure, less in the digital flow, and stronger in the peripheral vascular resistance than those without these findings of the heart and the aortic arch. 3. The curve of relationship obtained from many cases of both normotensives and hypertensives between the digital blood flow and the peripheral vascular resistance forms a hyperbola. 4. Peripheral vascular resistance in both normotensives and hypertensives increased gradually with age up to 50-60 years, and decreased slightly thereafter. The resistance was stronger in patients with essential hypertension than in normotensives through all ages.

Treatment of advanced renal cell carcinoma with a combination of human lymphoblastoid interferon-alpha and cimetidine.

Human lymphoblastoid interferon (IFN)-alpha was administered intramuscularly at doses of 5 megaunits/day 5 to 7 days a week to 32 advanced renal cell carcinoma patients. To augment the antitumor effect of IFN, cimetidine was also administered orally in doses oi 800 mg/day. This combination therapy resulted in a complete response (CR) in 6 patients (19%), a partial response (PR) in 7 (22%), a stable disease (SD) in 11 (34%), and a progressive disease (PD) in 8 (25%). The response rate (CR+PR) was 41%. The pulmonary metastases were more receptive to IFN therapy than those at other sites. The median times to response were 2 months for PR, and 4.5 months for CR. The survival of the responder patients was significantly longer than the nonresponder patients. These results suggest that IFN-alpha and cimetidine combination therapy may be of use in the management of advanced renal cell carcinoma.

[Transformation of the fungus ball type pulmonary aspergillosis].

Though the concept of semi-invasive pulmonary aspergillosis was advocated in 1981 by Gefter et al., its histopathological appearance has not yet been reported in detail. Pathological studies on fungus ball type pulmonary aspergillosis (PA) were originally made mainly in regard to related bronchi. Chronic-progressive destructive changes cannot be completely explained from this viewpoint alone. Clinically, since bloody sputum and hemoptysis appeared frequently, further studies on the pulmonary vasculature were considered necessary. In the resected lungs of 3 cases of semi-invasive pulmonary aspergillosis, the pathological features of pulmonary vasculature were characterized by numerous fungal clots within pulmonary arteries and veins, marked destruction of pulmonary blood vessels and extensive intravascular fibrin deposition. Intravascular fibrin deposition causes stasis of blood flow, promotes intravascular proliferation of aspergilli and probably accelerates pulmonary destruction caused by blood stasis. Important pathological findings of fungus ball type pulmonary aspergillosis of the semi-invasive subtype with clinical aspects of chronic-progressive lung destruction caused by severe inflammation, were reported for both the vascular and the bronchial system.

[Two cases of thalamic infarction presenting with "thalamic astasia"].

We report two cases of so-called 'thalamic astasia', associated with thalamic infarction. A 76-year-old-man suddenly noted to fall down to the left side without severe hemiparesis. An MRI showed an infarction in the superolateral portion of the right thalamus. Over eight weeks, his astasia gradually disappeared. A 69-year-old-man suddenly noted inability to stand with loss of balance. He showed mild hemiparesis, hypesthesia and cerebellar signs on the right side. Although right hemiparesis was slight, he was unable to stand by himself. An MRI demonstrated an infarction in the ventrolateral to ventroposterior portion of the left thalamus. Three weeks later, his symptoms except for cerebellar ataxia remarkably disappeared. The overlapped MRI lesions of these two cases were localized in the ventrolateral thalamus, such as Vimi (nucleus ventrointermedii internus), Vci (nucleus ventrocaudalis internus), Cemc (nucleus centralis thalami magnocellularis). These lesions are so-called 'vestibular thalamic nuclei', in which fibers from vestibulocerebellum are terminated. Involvement of the thalamic connectivity explains that two patients noted inability to stand. Thus we concluded that these two patients had thalamic astasia, described by Masdeu and Gorelick.