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Biomedical subjects

A Takaki

Publications and source records attributed to A Takaki.

At least 19 recordsLinked to original sources

[Evaluation of time dependency of the acetazolamide effect on cerebral hemodynamics as measured by 99mTc-ECD single-photon emission computed tomography].

PURPOSE: Kuwabara et al. have examined the cerebral artery dilation with acetazolamide (ACZ) challenge test using PET. And, they reported that ACZ reaction came out time dependently. We have developed a unique SPECT's method using Technetium-99m ethyl cysteinate dimer (99mTc-ECD) to verify the results obtained by Kuwabara et al. METHOD: 1000 MBq of 99mTc-ECD was exactly divided into three syringes. Each of which was intravenous infused (i.v.) at rest, 7.5, and 20 minutes after ACZ administration. Data collection was started using dynamic SPECT immediately after 99mTc-ECD i.v. at rest. Using necessary data only, SPECT images representing each of the three 99mTc-ECD i.v. was reconstructed. SPECT counts were obtained by the ROI method from each images to calculate relative CBF from rest to 7.5 and 20 minutes after ACZ administration. RESULT: The 18 hemispheres of nine patients in the negative control group in whom ACZ was not loaded. CBF was stable during the three evaluation. The measurement error our method was estimated as small. The 18 hemispheres of nine patients in the positive control group who has normal vasodilatory reserve, CBF was increased by 26.2 +/- 8.1% at 7.5 minutes and 29.3 +/- 13.1% at 20 minutes after ACZ administration. Seven patients with and chronic stage unilateral internal carotid artery severe stenosis and/or occlusion were evaluated as the test group. Case of unaffected side, CBF was increased by 17.6 +/- 6.9% at 7.5 minutes and 24.8 +/- 11.3% 20 minutes after ACZ administration. And, increase rate of CBF in the affected side was 2.8 +/- 1.6% at 7.5 minutes and 17.3 +/- 5.0% at 20 minutes after ACZ administration. In the affected side, timing of the maximum CBF increase caused by ACZ was remarkably delayed. CONCLUSION: Our method based on 99mTc-ECD SPECT also revealed delayed cerebral artery dilation in the affected side. It was suggested that ACZ reaction came out time dependently, as reported by Kuwabara et al.

Acetazolamide↗

[Accuracy and usefulness of ultraportable hand-carried echocardiography system].

OBJECTIVES: The diagnostic accuracy and usefulness of an ultraportable hand-carried echocardiography system were investigated for assessing ventricular systolic function and severity of mitral valvular regurgitation. METHODS: The study population consisted of 77 consecutive patients (47 men, 30 women, mean age 63 +/- 15 years). Left ventricular end-diastolic dimension, left ventricular end-systolic dimension and left ventricular ejection fraction were measured using the hand-carried echo system and the data were compared with measurements by the conventional echocardiography system using simple linear regression analysis. Left ventricular wall motion was compared between the systems using a 16-segment model recommended by the American Society of Echocardiography. Severity of mitral regurgitation was assessed by the distance of the regurgitant signal in the left atrium. RESULTS: Left ventricular end-diastolic dimension, left ventricular end-systolic dimension and left ventricular ejection fraction showed good correlations between hand-carried and conventional echo systems (r = 0.94, 0.91 and 0.81, respectively; each p < 0.0001). The accuracy for assessing left ventricular wall motion was 94% (449 of 480 segments). The echo systems also showed the same degree of diagnostic accuracy for severity of mitral regurgitation. CONCLUSIONS: The hand-carried echo system provides accurate assessment of left ventricular function and mitral regurgitation simular to conventional echo machines.

Aged↗

Cancer cell-targeted drug delivery utilizing oligopeptide transport activity.

To study the drug delivery to tumor by utilization of an oligopeptide transport activity, we examined the accumulation of dipeptides and the peptide-mimetic anti-cancer drug, bestatin, a substrate of oligopeptide transporter PepT1. Firstly, we established HeLa cells stably expressing human peptide transporter (hPepT1) (HeLa-hPepT1). Secondly, we constructed an experimental model by inoculation of HeLa-hPepT1 cells subcutaneously into Balb/c nu/nu mice to demonstrate the contribution of PepT1 to the tissue-selective drug delivery. The accumulations of a hydrolysis-resistant dipeptide [(3)H]carnosine and bestatin in solid tumors formed by HeLa-hPepT1 or HeLa-pcDNA3, which are transfected with vector DNA (pcDNA3) were measured. After I.V. administration, tissue-to-plasma concentration ratios (K(p)) of both compounds, in HeLa-hPepT1 tumor was significantly greater than that of [(14)C]inulin, a marker for extracellular fluid space, those of dipeptides in muscle, or those in HeLa-pcDNA3 tumor. Furthermore, bestatin exhibited growth inhibition of HeLa-hPepT1 in vitro. In vivo, repeated oral administration of bestatin for 28 days suppressed the growth of HeLa-hPepT1 tumor specifically. When HT-1080 cells, which may naturally express oligopeptide transport activity, were transplanted, K(p) of [(3)H]carnosine was significantly increased in comparison with that in muscle. In addition, oligopeptide transport activities among various human cell lines were examined. These results provide the first demonstration for the selective delivery of oligopeptides to tumors by specific oligopeptide transport activity.

Animals↗

Cellular immune responses persist and humoral responses decrease two decades after recovery from a single-source outbreak of hepatitis C.

As acute hepatitis C virus (HCV) infection is clinically inapparent in most cases, the immunologic correlates of recovery are not well defined. The cellular immune response is thought to contribute to the elimination of HCV-infected cells and a strong HCV-specific T-helper-cell (Th) response is associated with recovery from acute hepatitis C (ref. 2). However, diagnosis of resolved hepatitis C is based at present on the detection of HCV-specific antibodies and the absence of detectable HCV RNA, and detailed comparison of the humoral and cellular immune response has been hampered by the fact that patient cohorts as well as HCV strains are usually heterogeneous and that clinical data from acute-phase and long-term follow-up after infection generally are not available. We studied a cohort of women accidentally exposed to the same HCV strain of known sequence and found that circulating HCV-specific antibodies were undetectable in many patients 18-20 years after recovery, whereas HCV-specific helper and cytotoxic T-cell responses with an interferon (IFN)-gamma-producing (Tc1) phenotype persisted. The data indicate these HCV-specific CD4 + and CD8+ T cells are biomarkers for a prior HCV exposure and recovery. Because of undetectable antibodies against HCV, the incidence of self-limited HCV infections and recovery may be underestimated in the general population.

Antibody Specificity↗

Dietary nucleic acids promote a shift in Th1/Th2 balance toward Th1-dominant immunity.

BACKGROUND: Dietary sources of nucleic acids and their relative components are known to affect host immune function; however, it has not yet been clarified whether such dietary nucleic acids influence the pathogenesis of allergic reaction. OBJECTIVE: The purpose of this study is to elucidate the effect of dietary nucleic acids on Th1/Th2 balance. METHODS: Both human flora-associated and specific pathogen-free BALB/c mice were maintained on either nucleic acid-free, or -supplemented diets. The effects of nucleic acids on both in vivo antibody levels and in vitro splenocyte cytokine production were compared using these mice. RESULTS: Supplementation of nucleic acids caused a reduction in the serum antibody levels of total IgM, IgG, IgG1, and IgE in the human flora-associated mice without affecting the composition of intestinal flora. In contrast, there was no significant difference of the serum IgG2a levels between nucleic acid-free and -supplemented mice. Such a phenomenon as that, the supplementation of dietary nucleic acids reduces the serum IgE or IgG1 levels, but not the IgG2a level, was also seen in the specific pathogen free mice. Moreover, when the mice were systematically challenged with ovalbumin, the supplementation of nucleic acids also suppressed the serum ovalbumin-specific IgE and IgG1 antibody levels as well as in vitro IL-4 and IL-10 secretion, while enhancing both the serum ovalbumin-specific IgG2a antibody levels and in vitro IFN gamma secretion. CONCLUSION: These results suggested that dietary nucleic acids may play an important role in promoting a shift in Th1/Th2 balance toward Th1-dominant immunity.

Animals↗

Increase in CD95 (Fas/APO-1)-positive CD4+ and CD8+ T cells in peripheral blood derived from patients with autoimmune hepatitis or chronic hepatitis C with autoimmune phenomena.

BACKGROUND: The expressions of CD95 (Fas/APO-1) and Bcl-2 are determinants of apoptosis in normal lymphocytes, and abnormalities in their expressions might contribute to the induction of autoimmunity. In this study, we examined the expressions of CD95 and Bcl-2 on freshly isolated T and B cells from patients with autoimmune hepatitis (AIH) or chronic hepatitis C associated with autoimmune phenomena (CH-C(AI)). METHODS: The CD95 and Bcl-2 expressions within CD4+ T, CD8+ T, and CD19+ B cell subsets were analysed by two-colour flow cytometry. RESULTS: The surface expression of CD95 was significantly high in both the CD4+ T and CD8+ T cell subsets derived from the patients with AIH and those with CH-C(AI), compared with expression in patients with CH-C and normal subjects. The increase in CD95 expression was associated with the phenotypic conversion of naive CD45RO- to primed CD45RO+ CD4+ T cells. Bcl-2 was detected in the vast majority of peripheral T and B cells. There was no significant difference in the percentage of Bcl-2-positive cells in the CD4+ T cell, CD8+ T cell and CD19+ B cell subsets among the patient groups and normal subjects. CONCLUSIONS: These results indicate that an increase in CD4+ T cells expressing CD45RO and CD95 marks an important subset of AIH and CH-C(AI) patients. These expanded CD95+ CD45RO+ primed T cells most likely reflect a continuous antigen-specific or non-specific activation of T lymphocytes, and/or the persistent presence of activated lymphocytes as a consequence of abnormalities in the peripheral deletion of activated lymphocytes. These persistently activated lymphocytes might play a role in the induction of autoimmunity in AIH and CH-C(AI).

Adult↗

Cytological characterization of a pituitary folliculo-stellate-like cell line, Tpit/F1, with special reference to adenosine triphosphate-mediated neuronal nitric oxide synthase expression and nitric oxide secretion.

An immortal nonhormone-producing cell line with a characteristic star-shaped morphology, named Tpit/F1, was derived from an anterior pituitary gland of a temperature-sensitive large T antigen transgenic mouse. To characterize Tpit/F1 cells, we performed cytological studies, which revealed that Tpit/F1 cells express the messenger RNAs of neruonal nitric oxide (NO) synthase, S-100 protein, basic fibroblast growth factor, and pituitary-restricted transcription factor. The Tpit/F1 cells response to pituitary adenylate cyclase-activating peptide comprised the stimulated secretion of interleukin-6. Furthermore, glucocorticoids stimulate glutamine synthase production by Tpit/F1 cells. Considering these cytological characteristics together with their morphology, we deduced that Tpit/F1 cells are derived from pituitary folliculo-stellate (FS) cells. Our cytophysiological analyses of Tpit/F1 cells revealed that intracellular Ca2+ increased dose dependently on ATP administration (0-100 microM), and that this effect did not require the presence of extracellular Ca2+ and was not abolished by treatment with gadolinium, a Ca2+ channel blocker. The ATP-induced increase in intracellular Ca2+ ([Ca2+]i) was completely abolished by treatment with the Ca2+-adenosine triphosphatase (Ca2+-ATPase) inhibitor thapsigargin, which suggests that ATP increases [Ca2+]i by mobilizing internally stored Ca2+ followed by an influx of Ca2+. Moreover, UTP was equipotent with ATP in causing the [Ca2+]i increase in Tpit/F1 cells. Also, the Ca2+ response was prevented by the phospholipase C inhibitor, U-73122, but not by its inactive analog, U-73343. From these results we therefore concluded that ATP acts on Tpit/F1 cells via P2Y2-purinoceptors. Interestingly, both neuronal nitric oxide synthase messenger RNA and NO secretion were increased by ATP administration (10 and 100 microM). These results suggest the biological significance of the topological colocalization of FS cells and endocrine cells. Namely, ATP is cosecreted with hormones from endocrine cells and stimulates NO production by FS cells, and the released NO may regulate neighboring endocrine cell and blood vessels.

Adenosine Triphosphate↗

Fatal severe vasospasm due to rewarming following hypothermia--case report.

A 37-year-old female died of cerebral vasospasm as a complication of rewarming following hypothermia therapy for severe head injury. She presented with severe consciousness disturbance and anisocoria after falling down a flight of stairs. Computed tomography (CT) revealed a right acute subdural hematoma and temporal contusion. Following surgery, mild hypothermia was started and rewarming was completed by the 11th day. Neurological examination showed no abnormalities, but intracranial pressure (ICP) suddenly increased and she manifested anisocoria on the 13th day. Repeat CT revealed a low density area in the right middle cerebral artery region and cerebral angiography showed diffuse narrowing of the main arterial trunks. A cerebrospinal fluid (CSF) sample was collected using an intraventricular ICP monitoring catheter. The CSF level of 8-hydroxy-2'-deoxyguanosine was elevated during the rewarming period, indicating substantial deoxyribonucleic acid (DNA) oxidation. She died on the 15th day due to uncontrollable ICP. Histological examination at autopsy of the narrowed artery found the waving phenomenon in the internal elastic lamina and invasion of inflammatory cells into the adventitia. These findings constitute the possible evidence that free-radical-mediated oxidative DNA damage may be important in the genesis of severe vasospasm due to rewarming following hypothermia.

Adult↗

[Different responses of right and left ventricular diastolic function to pulmonary resection: echocardiographic study with leg elevation for preload augmentation].

OBJECTIVES: The effects of pulmonary resection on cardiac function have not been well characterized. This study used Doppler echocardiography to evaluate preoperative and postoperative right and left ventricular function with preload augmentation by elevation of the legs. METHODS: Twenty-one patients (12 males, 9 females, mean age 64 +/- 11 years) undergoing pulmonary resection for lung cancer underwent concurrent examination of cardiac and pulmonary function at 1 week preoperation and 4 weeks postoperation. Cardiac function of right and left ventricles was assessed by Doppler echocardiography to record waveforms of transtricuspid flow and transmitral flow. Assessment was made in the supine position and with leg elevation 60 degrees to apply preload augmentation. We measured the interval between cessation and onset of transatrioventricular flow, ventricular ejection time and Tei index as an index of global ventricular function. Peak velocity of early filling (E) and atrial contraction (A) were measured from the transtricuspid and transmitral flows to calculate E/A of the right and left ventricles (ER/AR, EL/AL). Pulmonary function tests yielded the forced vital capacity expressed as the ratio to the predicted value as an index for the pulmonary vascular bed area. RESULTS: The postoperative cardiac function without preload augmentation was comparable to the preoperation function. With preload augmentation, the postoperative ER/AR was less than preoperation in the patients with postoperative forced vital capacity < or = 80% of the preoperation value. There was a significant correlation between the postoperation versus preoperation ratio of ER/AR and of forced vital capacity (r = 0.66, p = 0.0028) and ratio of right ventricular Tei index and of forced vital capacity (r = 0.61, p = 0.0034). There was a possibility that right ventricular Tei index indirectly indicated the state of pulmonary vascular bed area. CONCLUSIONS: The right ventricular Tei index is useful to estimate preoperation and postoperation global right ventricular function. No close relationship between ER/AR and EL/AL at preoperation (r = 0.70, p = 0.0004) was found in the patients with postoperative right ventricular Tei index > 0.1 greater than at preoperation. Pulmonary resection might affect the diastolic function of the right ventricle more than the left ventricle, possibly because of reduced compliance of the right ventricle indicated by an increased atrial contraction at postoperation with preload augmentation.

Diastole↗

[Technical investigation of cerebral blood flow measurements using the Patlak Plot method--a contrivance for positioning of the gamma camera at data collection in radionuclide angiography].

The time-activity curve for the aortic arch obtained from radionuclide angiography (RNA) is handled as an input function parameter according to the method of Matsuda et al., which determines regional cerebral blood flow non-invasively. The data are collected from a frontal view of the thorax captured by RNA by their method, however we encountered a case in which it was difficult to identify aortic arch in the data collection from the frontal view. The precise identification of the aortic arch was implemented when the RNA data were collected from the left anterior oblique view of the thorax. No significant difference was noted in the measured values between the data collection from the frontal view and from the left anterior oblique view. Our method seems to be useful modification of the Patlak plot method.

Aged↗

[Reduction of the influence of the liver uptake to the myocardial uptake on technetium-99m myocardial SPECT; usefulness and problems of a mask processing method].

The aim of this study is to evaluate the usefulness of a mask processing method for obtaining the true myocardial tracer distribution by eliminating the influence of the liver uptake to the myocardial uptake on myocardial SPECT images by using technetium-99m (99mTc) blood flow agents. A SPECT imaging was performed with a two-head SPECT system (GCA-7200A/DI) in both phantom and clinical studies. The mask processing method was applied to the reconstructed and projection images. The phantom consisted of heart, lung, liver and spine. A defect was located in the inferior wall of the left ventricle and other parts of the heart and liver were filled with 99mTc solution. For clinical study 10 patients with difficulty in the interpretation of the inferior wall were selected for the evaluation of usefulness of the mask method. In the phantom study, the mask processing method applied to the reconstructed images was able to remove the overlapped liver from the heart, but was not able to remove the influence of the liver uptake to the myocardial uptake. Nevertheless, the mask processing method applied to the projection images successfully eliminated not only the overlapped liver but also the influence of the liver uptake to the myocardial uptake. In the clinical study, the liver uptake could be removed from the uptake in the inferior wall in 8 of 10 patients with the mask processing methods. In 2 patients, the overlapped liver uptake could not be eliminated from the uptake in the inferior wall because the distance between the liver and heart was too short. The mask processing method applied to the projection images was thought to be superior to that applied to the reconstruction images in both phantom and clinical studies. The mask processing method, especially applied to the projection images, seems to be useful for the elimination of the liver uptake from the inferior wall of the myocardium on myocardial SPECT images using 99mTc blood flow agents.

Artifacts↗

PACAP protects hippocampal neurons against apoptosis: involvement of JNK/SAPK signaling pathway.

We have demonstrated that the ischemia-induced apoptosis of neurons in the CA1 region of the rat hippocampus was prevented by either intracerebroventricular or intravenous infusion of pituitary adenylate cyclase-activating polypeptide (PACAP). However, the molecular mechanisms underlying the anti-apoptotic effect of PACAP remain to be determined. Within 3-6 h after ischemia, the activities of members of the mitogen-activated protein (MAP) kinase family, including extracellular signal-regulated kinase (ERK), Jun N-terminal kinase (JNK)/stress-activated protein kinase (SAPK), and p38 were increased in the hippocampus. The ischemic stress had a potent influence on the MAP kinase family, especially on JNK/SAPK. PACAP inhibited the activation of JNK/SAPK after ischemic stress. Secretion of interleukin-6 (IL-6) into the cerebrospinal fluid was intensely stimulated after PACAP infusion. IL-6 inhibited the activation of JNK/SAPK, while it activated ERK. These observations suggest that PACAP and IL-6 act to inhibit the JNK/SAPK signaling pathway, thereby protecting neurons against apoptosis.

Animals↗

AV3V neurons that send axons to hypothalamic nuclei respond to the systemic injection of IL-1beta.

The single neuron activity in the anteroventral region of the third ventricle (AV3V) was extracellularly recorded in urethan and alpha-chloralose anesthetized rats. Electrical stimulation of the medial preoptic area (mPOA) and the paraventricular nucleus (PVN) revealed a reciprocal neural connection between the AV3V and these hypothalamic nuclei with an ipsilateral preponderance. All the AV3V neurons, which were antidromically activated by the stimulation of the mPOA or the PVN, altered their activity after the systemic injection of interleukin (IL)-1beta. On the other hand, only about 60% of the AV3V neurons that showed orthodromic responses were affected by IL-1beta. In seven of nine AV3V neurons that were electrophysiologically identified to send their axons to the mPOA or the PVN, the recombinant human IL-1beta-induced excitation and inhibition were attenuated by a local application of sodium salicylate through multibarreled micropipettes. These results suggest that the AV3V neurons alter their activity in response to the blood-borne IL-1beta, at least in part, through a local synthesis of prostanoids and then send the information to the mPOA and PVN.

Animals↗

Central noradrenergic system modulates plasma interleukin-6 production by peripheral interleukin-1.

The role of the central noradrenergic system in systemic interleukin-6 (IL-6) production induced by intravenously administered recombinant human interleukin-1 beta (IL-1 beta) was examined in rats. Pretreatment of rats intracerebroventricularly with 6-hydroxydopamine (6-OHDA, 100 or 200 micrograms/rat) significantly attenuated the increase in plasma IL-6 levels caused by IL-1 beta (2 micrograms/kg i.v.). A modest inhibition of the IL-1 beta-induced plasma IL-6 production was observed following pretreatment with prazosin (20 micrograms/rat i.c.v.) but not after administration of idazoxan or propranolol. There were no significant increases in the IL-6 content in the hypothalamus, medulla oblongata, and cortex of the brain after intravenous IL-1 beta. Adrenalectomy produced an augmented plasma IL-6 response to intravenous IL-1 beta, whereas chemical sympathectomy with intraperitoneal injection of 6-OHDA (50 or 100 mg/kg) decreased the IL-1 beta-induced plasma IL-6 levels. Nor-epinephrine (NE), in the dose range 10(-6)-10(-4) M, significantly increased the IL-6 levels in the rat spleen lymphocyte culture media. At doses of 10(-9)-10(-7) M, NE enhanced the effect of IL-1 beta on the IL-6 release by spleen lymphocytes in a dose-dependent manner. These findings suggest that the plasma IL-6 response to intravenous IL-1 beta is partially mediated through the activation of the central noradrenergic system and a consequent increase in the sympathetic outflow to the peripheral tissues and that the NE released from the sympathetic terminals may function as a mediator and/or modulator to facilitate the synthesis/release of IL-6 in the sympathetic nerve-innervated organs.

Adrenergic Antagonists↗

Assessment of pulmonary venous and transmitral flow in closed-chest dogs under various loading conditions by transesophageal Doppler echocardiography.

Pulmonary venous flow velocity (PVFVe), pulmonary venous dimension (PVD) and transmitral flow (TMF) velocity were examined under various loading conditions in 15 anesthetized closed-chest dogs by transesophageal Doppler echocardiography (TEE). We also compared PVFVe with pulmonary venous flow volume (PVFVo) simultaneously in open-chest dogs using an ultrasonic flow probe. PVFVo decreased by more than 50% and PVD also decreased significantly during preload reduction, while there was no change in PVFVe. This discrepancy between PVFVo and PVFVe was apparently due to the collapse of pulmonary veins. TMF consisted of both rapid-filling flow velocity and atrial flow velocity components (R and A), while PVF consisted of systolic and diastolic forward flow velocity components (S and D). The peak values of R,A,S and D and the time-velocity integrals of each wave (RI, AI, SI and DI, respectively) were measured. There was a significant correlation between the changes in RI and SI/DI during preload reduction (r = 0.82, p < 0.001) and during after-load increase (r = -0.59, p < 0.05). These results suggest that changes in RI with different loading conditions might be attributable to changes in atrial reservoir volume and conduit volume.

Animals↗

Specificities and clinical significance of anti-cytoskeleton antibodies in anti-smooth muscle antibody-positive patients with chronic liver disease C.

We investigated the specificities and characteristics of anti-cytoskeleton antibodies in 13 anti-smooth muscle antibody (ASMA)-positive patients with chronic liver disease C (CLD-C), and compared them with those in 7 ASMA-positive patients with autoimmune hepatitis (AIH), and 6 ASMA-positive patients with chronic liver disease B (CLD-B). Anti-microfilaments (anti-MF) were found not only in 6/7 AIH patients (85.7%), but also in 8/13 CLD-C patients (61.5%) with a relatively high incidence, when compared with 1/6 CLD-B patients (16.7%), while, there was no significant difference in the incidence of anti-intermediate filaments (anti-IMF), especially anti-IMF IgM, among these patient groups. Among the patients with CLD-C, the mean levels of serum gammaglobulin and IgG in the anti-MF-positive patients were 2.46 +/- 1.03 g/dl and 3277 +/- 1089 mg/dl, respectively, which were higher than those in the anti-MF-negative patients (1.60 +/- 0.53 g/dl, 2245 +/- 610 mg/dl) and those in the patients with CLD-B (1.60 +/- 0.57 g/dl, 2192 +/- 339 mg/dl). Furthermore, 4 of the 8 anti-MF-positive patients with CLD-C satisfied the serological criteria for the diagnosis of AIH. These findings suggest that autoimmune mechanisms might be involved in the pathogenesis of anti-MF-positive CLD-C, and that anti-MF might be used as a marker.

Adult↗

Disappearance of pulmonary metastases by OK-432 treatment in a case of hepatocellular carcinoma.

We report here a case of hepatocellular carcinoma (HCC) with multiple lung metastases, which were disappeared by treatment of OK-432. The patient was a 65-year-old man and was diagnosed in 1986 with a small (17 x 11 mm) HCC in the anterior-superior segment of the liver. A part of the right hepatic lobe including the tumor was surgically removed, and transarterial injections of adriamycin (10 mg/week) and subcutaneous injections of OK-432 (10 KE/week) were given. Two and a half years later, recurrence of HCC in the liver and its invasion to vena cava inferior (IVC) were found. OK-432 administration was then stopped and percutaneous ethanol injection therapy (PEIT) was performed 10 times. Six months later, the PEIT was effective and the liver tumor with IVC invasion diminished. However, multiple lung metastases were visible on roentgenograms of the chest, and serum alphafetoprotein (AFP) concentration increased to 50,000 ng/ml. The OK-432 treatment resumed. After 6 months of OK-432 treatment, the multiple lung metastases were disappeared and the serum AFP level decreased to 100 ng/ml. At present, the patient is surviving without any sign of recurrence in either the liver or the lung. The clinical course of this case suggests that OK-432 might have effectively treated lung metastases of HCC, although the exact mechanisms are at present unclear.

Aged↗