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Purpose: To describe clinical presentations of acquired comitant esotropia and digital device use in children, adolescents, and young adults without neurological problems., Study Design: Multicenter prospective observational study., Methods: Patients with acquired comitant esotropia, without intracranial diseases aged 5-35 years at the time of visit, who were seen at pre-registered facilities within 1 year of onset were enrolled. The duration from the onset of symptoms and the time of digital device usage approximately 1 month before onset and their lifestyles were surveyed. Visual acuity, cycloplegic refraction, and strabismus angles were measured. Data were analyzed in three age groups (Child: 5-12 years, Adolescent: 13-18 years, and Young adult: 19-35 years)., Results: Between November 2019 and December 2021, 218 patients were enrolled from 55 facilities, and 194 patients (including 62 children, 69 adolescents, and 63 young adults) were analyzed. The child group spent the least amount of time using digital devices (children: 159; adolescents: 210; young adults: 267 min/work day, p < 0.05; (mean time in the same order below) 229, 338, 314 min/holiday, p < 0.05) and had the largest strabismus angle (mean strabismus angle at near: 30, 22, 18 PD, p < 0.01; at far: 28, 26, 21 PD, p<0.05)., Conclusion: The clinical features of acquired comitant esotropia and hand-held digital device usage differed between children aged ≤ 12 years and older patients. This report gives the current clinical characteristics of young patients with acquired esotropia and digital device usage., (© 2023. Japanese Ophthalmological Society.)

Purpose: Integrin α v is a key regulator in the pathophysiology of hepatic fibrosis. In this study, we evaluated the potential utility of an integrin α v β 3 positron emission tomography (PET) radiotracer, 18 F-labeled cyclic arginine-glycine-aspartic acid penta-peptide ([ 18 F]F-FPP-RGD 2 ), for detecting hepatic integrin α v and function in nonalcoholic steatohepatitis (NASH) model rats using integrin α v siRNA., Methods: NASH model rats were produced by feeding a choline-deficient, low-methionine, high-fat diet for 8 weeks. PET/computerized tomography imaging and quantification of integrin α v protein, serum aspartate aminotransferase, and alanine aminotransferase were performed 1 week after single intravenous injection of integrin α v siRNA., Results: Integrin α v siRNA (0.1 and 0.5 mg/kg) dose-dependently decreased hepatic integrin α v protein concentrations in control and NASH model rats. The hepatic mean standard uptake value of [ 18 F]F-FPP-RGD 2 was decreased dose-dependently by integrin α v siRNA. The mean standard uptake value was positively correlated with integrin α v protein levels in control and NASH model rats. Serum aspartate aminotransferase and alanine aminotransferase concentrations were also decreased by siRNA injection and correlated with liver integrin α v protein expression levels in NASH model rats., Conclusion: This study suggests that [ 18 F]F-FPP-RGD 2 PET imaging is a promising radiotracer for monitoring hepatic integrin α v protein levels and hepatic function in NASH pathology., Competing Interests: Conflict of InterestShuichi Hiroyama, Keiko Matsunaga, Miwa Ito, Hitoshi Iimori, Ippei Morita, Jun Nakamura, Eku Shimosegawa, and Kohji Abe declare that they have no competing interests., (© The Author(s), under exclusive licence to Korean Society of Nuclear Medicine 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Purpose: Integrins α v are key molecules in the pathogenesis of fibrosis in multiple organs. To assess the potential utility of integrin α v β 3 imaging for idiopathic pulmonary fibrosis (IPF), we evaluated an 18 F-FPP-RGD 2 PET probe in a rat model of bleomycin-induced lung fibrosis., Methods: Pulmonary fibrosis was induced by single intratracheal instillation of bleomycin (3 mg/rat). Positron emission tomography (PET)/computerized tomography scans were performed 4 weeks after bleomycin administration using 18 F-FPP-RGD 2 . Total distribution volume (V T ) was estimated using one-tissue/two-compartment, two-tissue/three-compartment models, and Logan graphical analysis (Logan plot; t* = 30 min). Plasma-free fractions were estimated from images of the left ventricle. Correlation between Logan V T and lung pathology was assessed by Spearman's rank correlation., Results: Histopathological evaluation demonstrated the development of fibrosis in IPF-model group. Integrin α v protein expression and lung radioactivity were higher in IPF-model group compared with control group. The lung radioactivity of 18 F-FPP-RGD 2 rapidly reached the peak after administration and then gradually decreased, whereas left ventricular radioactivity rapidly disappeared. Logan graphical analysis was found to be suitable for 18 F-FPP-RGD 2 kinetic analysis in the IPF-model lung. Logan V T values for 18 F-FPP-RGD 2 were significantly higher in IPF rats compared with control rats and strongly correlated with lung fibrosis, pathology, integrin α v protein expression, and oxygen partial pressure., Conclusion: Our findings demonstrate that the integrin α v β 3 PET probe 18 F-FPP-RGD 2 can detect pathophysiological changes in lungs, including fibrosis accompanying upregulated integrin α v of IPF-model rats. These findings support the utility of 18 F-FPP-RGD 2 PET imaging for the pathophysiological evaluation of pulmonary fibrosis., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: This study aimed to identify the characteristics of acute acquired comitant esotropia (AACE) in young patients from a single institution; and clarify their relationship with the excess use of digital devices., Study Design: Retrospective, observational., Methods: We extracted the clinical charts of patients aged between 5 and 35 years who presented at the Hamamatsu University Hospital with AACE symptoms from January 1, 2015 to December 31, 2018. The age of onset, angle of deviation, refractive errors, history of near work, including excess smartphone use, and treatment modality were retrieved. Patients were divided into three groups: CHILD (aged 5-12 years), JUNIOR (aged 13-17 years), and ADULT (aged 18-35 years) and statistically analyzed with Kruskal-Wallis test., Results: Forty-one patients were retrieved, with a mean age at onset of 15.8 (5-28) years; eight in the CHILD group, 23 in the JUNIOR group, and 10 in the ADULT group. Refractive errors and age of patients were correlated, but were not significantly different among groups. The mean angle of deviation at distance was 28.0 ± 12.8 prism diopters (PD) and 28.6 ± 17.2 PD at near. The CHILD group showed the largest near-distant dissociation. History of excessive near work was found in all groups., Conclusion: AACE was most commonly found in the JUNIOR group, especially those aged 15-16 years. AACE may encompass multiple diseases; using common diagnostic criteria and asking common questions regarding digital device usage is necessary to clarify the influence of digital device usage, and a multicenter prospective study is recommended., (© 2021. Japanese Ophthalmological Society.)

Pharmacological magnetic resonance imaging (phMRI) allows the visualization of brain pharmacological effects of drugs using functional MRI (fMRI). phMRI can help us facilitate central nervous system (CNS) drug development. However, there have been few studies demonstrating the dose relationship of the fMRI response induced by CNS drugs to underlying target engagement or behavioral efficacy. To clarify these relationships, we examined receptor occupancy measurements using positron emission tomography (PET) (n = 3~5), fMRI (n = 5~8) and a cataleptic behavior (n = 6) with raclopride, a dopamine D2 receptor antagonist (8, 20, and 200 μg/kg) on Wistar rats. Dopamine D2 receptor occupancy was increased dose dependently by raclopride (41.8 ± 2.7%, 8 μg/kg; 64.9 ± 2.8%, 20 μg/kg; 83.1 ± 3.0%, 200 μg/kg). phMRI study revealed significant positive responses to raclopride at 200 μg/kg specifically in the striatum and nucleus accumbens, related to dopaminergic system. Slight fMRI responses were observed at 20 μg/kg in some areas corresponding to the striatum and nucleus accumbens. There were no noticeable fMRI responses at 8 μg/kg raclopride administration. Raclopride at 200 μg/kg significantly increased the cataleptic score, although, at 8 and 20 μg/kg, raclopride had no significant effects. These findings showed that raclopride-induced fMRI responses were observed at doses inducing cataleptic behavior and high D2 receptor occupancy, suggesting that phMRI can be useful for dose selection in clinical trial as an evaluation method of brain activity, which reflects behavioral responses induced by target engagements., (© 2020 Wiley Periodicals LLC.)

Background: Integrin α v β 3 , which are expressed by activated hepatic stellate cells in non-alcoholic steatohepatitis (NASH), play an important role in the fibrosis. Recently, we reported that an RGD peptide positron emission tomography (PET) probe is useful as a predictor of hepatic fibrosis. Kinetic analysis of the RGD PET probe has been performed in tumours, but not in hepatic fibrosis. Therefore, we aimed to quantify hepatic integrin α v β 3 in a model of NASH by kinetic analysis using 18 F-FPP-RGD 2 , an integrin α v β 3 PET probe., Methods: 18 F-FPP-RGD 2 PET/CT scans were performed in control and NASH rats. Tissue kinetic analyses were performed using a one-tissue, two-compartment (1T2C) and a two-tissue, three-compartment (2T3C) model using an image-derived input function (IDIF) for the left ventricle. We then conducted correlation analysis between standard uptake values (SUVs) or volume of distribution (V T ), evaluated using compartment kinetic analysis and integrin α v or β 3 protein expression., Results: Biochemical and histological evaluation confirmed the development of NASH rats. Integrin α v β 3 protein expression and hepatic SUV were higher in NASH- than normal rats. The hepatic activity of 18 F-FPP-RGD 2 peaked rapidly after administration and then gradually decreased, whereas left ventricular activity rapidly disappeared. The 2T3C model was found to be preferable for 18 F-FPP-RGD 2 kinetic analysis in the liver. The V T (IDIF) for 18 F-FPP-RGD 2 , calculated using the 2T3C model, was significantly higher in NASH- than normal rats and correlated strongly with hepatic integrin α v and β 3 protein expression. The strengths of these correlations were similar to those between SUV 60-90 min and hepatic integrin α v or β 3 protein expression., Conclusions: We have demonstrated that the V T (IDIF) of 18 F-FPP-RGD 2 , calculated using kinetic modelling, positively correlates with integrin α v and β 3 protein in the liver of NASH rats. These findings suggest that hepatic V T (IDIF) provides a quantitative assessment of integrin α v β 3 protein in liver.

Background: Translocator protein (TSPO) imaging can be used to detect neuroinflammation (including microglial activation) after acute cerebral infarction. However, longitudinal changes of TSPO binding after mild ischemia that induces selective neuronal loss (SNL) without acute infarction are not well understood. Here, we performed TSPO imaging with [ 18 F]DPA-714 to determine the time course of neuroinflammation and SNL after mild focal ischemia., Results: Mild focal ischemia was induced by middle cerebral artery occlusion (MCAO) for 20 min. In MCAO rats without acute infarction investigated by 2, 3, 5-triphenyltetrazolium chloride (TTC) staining, in vitro ARG revealed a significant increase of [ 18 F]DPA-714 binding in the ipsilateral striatum compared with that in the contralateral side at 1, 2, 3, and 7 days after MCAO. Increased [ 18 F]DPA-714 binding was observed in the cerebral cortex penumbra, reaching maximal values at 7 days after MCAO. Activation of striatal microglia and astrocytes was observed with immunohistochemistry of ionized calcium binding adaptor molecule 1 (Iba1) and glial fibrillary acidic protein (GFAP) at 2, 3, and 7 days after MCAO. SNL was investigated with Nissl staining and neuronal nuclei (NeuN) immunostaining and observed in the ischemic core region of the striatum on days 3 and 7 after MCAO. We confirmed that total distribution volume of [ 18 F]DPA-714 in the ipsilateral striatum was significantly increased at 2 and 7 days after MCAO using positron emission tomography (PET)., Conclusions: [ 18 F]DPA-714 binding measured with in vitro ARG was increased before SNL appeared, and this change was detected by in vivo PET. These findings suggest that TSPO PET imaging might be useful for detection of neuroinflammation leading to SNL after focal ischemia.

Background: Activated hepatic stellate cells (HSCs), which express integrin αvβ3, are a major fibrogenic factor in NASH pathophysiology. 18 F-labeled cyclic arginine-glycine-aspartic acid penta-peptide ( 18 F-FPP-RGD 2 ) has been used as a PET probe for tumors expressing integrin αvβ3. The aim of this study was to assess the potential of PET with 18 F-FPP-RGD 2 to detect hepatic integrin αvβ3 expression in non-alcoholic steatohepatitis (NASH) model mice., Results: Thirty-two male C57BL/6 mice aged 6 weeks were fed a choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD) for 3 and 8 weeks. 18 F-FPP-RGD 2 PET imaging of the liver was performed at 3 and 8 weeks after CDAHFD feeding. After PET scanning, levels of hepatic integrin αvβ, 3α-smooth muscle actin (α-SMA), and collagen type 1 alpha 1(col1a1) were measured. Histopathological analysis of hepatic steatosis, inflammation, and fibrosis, as well as blood biochemistry analysis, was also performed. CDAHFD for 3 and 8 weeks produced a moderate-to-severe steatosis and inflammation of the liver in mice. NAFLD activity score (NAS) in mice fed the CDAHFD for 3 and 8 weeks were more than 4 indicating NASH or borderline NASH pathology. Fibrosis was observed only in mice fed the CDAHFD for 8 weeks. PET imaging showed that the hepatic standardized uptake value, SUV 80-90 min , was increased with prolonged CDAHFD feeding compared with the respective controls (CDAHFD 3 weeks 0.32 ± 0.06 vs 0.48 ± 0.05, p < 0.01; CDAHFD 8 weeks 0.35 ± 0.04 vs 0.75 ± 0.07, p < 0.01, respectively). Prolonged CDAHFD feeding increased hepatic mRNA and protein levels of integrin αv and β3 at 3 and 8 weeks. Hepatic 18 F-FPP-RGD 2 uptake and amount of integrin αv and β3 protein were well correlated (r = 0.593, p < 0.05 and r = 0.835, p < 0.001, respectively). Hepatic 18 F-FPP-RGD 2 uptake also showed a positive correlation with Sirius red-positive area., Conclusions: The hepatic uptake of 18 F-FPP-RGD 2 correlated well with integrin αv and β3 expression and histological fibrosis in a mouse model of NASH, suggesting the predictability of fibrosis in NASH pathology.

Background: Mitochondrial dysfunction is one of the main causes of non-alcohol fatty liver disease (NAFLD). [ 18 F]-BMS-747158-02 ( 18 F-BMS) which was originally developed as a myocardial perfusion imaging agent was reported to bind mitochondrial complex-1 (MC-1). The aim of this study was to investigate the potential use of 18 F-BMS for evaluating hepatic MC-1 activity in mice fed a methionine- and choline-deficient (MCD) diet. Male C57BL/6J mice were fed a MCD diet for up to 2 weeks. PET scans with 18 F-BMS were performed after 1 and 2 weeks of the MCD diet. 18 F-BMS was intravenously injected into mice, and the uptake (standardized uptake value (SUV)) in the liver was determined. The binding specificity for MC-1 was assessed by pre-administration of rotenone, a specific MC-1 inhibitor. Hepatic MC-1 activity was measured using liver homogenates generated after each positron emission tomography (PET) scan. Blood biochemistry and histopathology were also assessed., Results: In control mice, hepatic 18 F-BMS uptake was significantly inhibited by the pre-injection of rotenone. The uptake of 18 F-BMS was significantly decreased after 2 weeks of the MCD diet. The SUV at 30-60 min was well correlated with hepatic MC-1 activity (r = 0.73, p < 0.05). Increases in plasma ALT and AST levels were also noted at 1 and 2 weeks. Mild hepatic steatosis with or without minimal inflammation was histopathologically observed at 1 and 2 weeks in mice liver on the MCD diet. However, inflammation was observed only at 2 weeks in mice on the MCD diet., Conclusions: The present study demonstrated that 18 F-BMS is a potential PET probe for quantitative imaging of hepatic MC-1 activity and its mitochondrial dysfunction induced by steatosis and inflammation, such as in NAFLD.

The changes in the availability of striatal dopamine transporter and dopamine D2 receptor after mild focal ischemia in rats were measured using a small animal positron emission tomography system. Mild focal ischemia was induced by 20-minute middle cerebral artery occlusion. [ 11 C]PE2I binding to dopamine transporter was transiently increased on the ipsilateral side of the striatum at 2 days after middle cerebral artery occlusion. On day 7 and 14 after middle cerebral artery occlusion, [ 11 C]PE2I binding levels were decreased. In contrast, [ 11 C]raclopride binding to dopamine D2 receptor in the ipsilateral striatum had not changed at 2 days after middle cerebral artery occlusion. [ 11 C]Raclopride binding was significantly decreased on the ischemic side of the striatum at 7 and 14 days after middle cerebral artery occlusion. Moreover, on day 1 and 2 after middle cerebral artery occlusion, significant circling behavior to the contralateral direction was induced by amphetamine challenge. This behavior disappeared at 7 days after middle cerebral artery occlusion. At 14 days, circling behavior to the ipsilateral direction (middle cerebral artery occlusion side) was significantly increased, and that to the contralateral direction also appeared again. The present study suggested that amphetamine-induced circling behavior indicated striatal dopaminergic alterations and that dopamine transporter and dopamine D2 receptor binding could be key markers for predicting motor dysfunction after mild focal ischemia.

Objective: Telmisartan, a nonpeptide angiotensin II AT1 receptor antagonist, is an antihypertensive drug. Positron emission tomography (PET) imaging with [(11)C]Telmisartan is expected to provide information about the whole body pharmacokinetics of telmisartan as well as the transport function of hepatic OATP1B3. We developed a first automatic preparation system of [(11)C]Telmisartan to applicable clinical research using a new (11)C and (18)F multipurpose synthesizer., Methods: Two milligrams of precursor (1) in 5 μl of 1 M KOH in 0.5 ml of dimethyl sulfoxide was reacted with [(11)C]CH(3)I for 5 min at 120°C. The resultant solution was hydrolyzed with 1 M NaOH at 100°C for 3 min. The neutralization was carried out with acetic acid, followed by purification with high-performance liquid chromatography. The desired radioactive fraction was collected and solvent was replaced by 10 ml saline containing 0.3 ml of EtOH and 0.5 ml of PEG400, and then passed through a sterile 0.22 μm filter (Millex-GV, Millipore) to a pyrogen-free vial as the final product., Results: The yield of [(11)C]Telmisartan for clinical research use was 16.8 ± 2.9% EOB as decay corrected (n = 8, mean ± SD) in 32-36 min. The radiochemical purity of [(11)C]Telmisartan was >97%, and specific activity was higher than 86.3 MBq/nmol., Conclusions: We succeeded in the first synthesis of [(11)C]Telmisartan for clinical research use by appropriate quality tests.

Social support is supposed to have a positive health effect via alteration of immunity. In this study, associations between perceived social support and immune systems were examined. Immunological assessments, e.g. T cell count, Natural Killer cell count, Interferon-gamma, Interleukin-4, and psychological assessments, e.g. Generic Job Stress Questionnaire were conducted on male employees. Two-way (social support x job stressor) analyses of covariance controlling for age, smoking, alcohol consumption, and exercise revealed that there were main effects of perceived social support on NK cell counts, IL-4, and Th1/Th2 balance. On the other hand, interaction effects were observed on T cell counts and INF-gamma production in vitro. Social support affects immune function in a way that is consistent with both the direct and buffering hypotheses depending on the sources of support and the immune parameter.

Mercaptoacetyliminothiadiazoline derivatives (19, 20) useful for the pendant moiety of 1beta-methylcarbapenem antibiotics were efficiently synthesized. Acetyl derivative (18) of 20 was submitted to X-ray analysis, and a significant nonbonded S...O close contact was recognized in the crystallographic structure. New 1beta-methylcarbapenems (5, 6) were synthesized by exploiting 19 and 20, and exhibited considerable antibacterial activities in vitro.

Objective: The lateral hypothalamic area (LHa) is involved in various functions such as feeding, drinking, sexual and reward behavior, among others. Recently, we demonstrated that the LHa can regulate cellular immunity in the spleen. In experiments involving the LHa, it was noticed that the spleen shrinks noticeably after LHa destruction. To explore this phenomenon further, the effect of LHa lesioning on splenocyte apoptosis was investigated., Methods: Male Wistar-King-Aptekman rats underwent bilateral lesioning of their LHa and consequent spleen weights, splenocyte numbers and apoptosis were measured. For the detection of splenocyte apoptosis, both ELISA, which measures DNA fragmentation within the splenocytes, and flow cytometry, which measures the percentage of apoptotic lymphocytes in the spleen, were used., Results: In the LHa-lesioned rats, spleen weights and the number of splenocytes decreased significantly within 24 h. Additionally, in the spleen, lymphocyte apoptosis significantly increased compared to the control after 6 h., Conclusion: These results suggest that the LHa may play a role in immunoregulation by affecting lymphocytes in the spleen through apoptosis and may be relevant to the pathway of stress-induced apoptosis., (Copyright 2001 S. Karger AG, Basel.)

Electrical stimulation of the lateral hypothalamus (LH) in rats increased splenic natural killer (NK) cell activity, whereas electrical ablation of the LH decreased it. However, the percentage of NK cells, as detected by the anti-NKR-P1 monoclonal antibody, in the spleen did not change significantly. These results suggest that the LH does not modulate the splenic NK cell activity by increasing the NK cell number but by increasing the intrinsic NK cell activity itself.

Background: We performed macro and micro-autoradiographic studies using 14C-oxalate in normal and hyperoxaluric rats in order to elucidate intrarenal distribution of oxalate and to determine where calcium oxalate crystal can be adhere in the kidney., Methods: Macro and micro-autoradiographic studies of the kidney in normal rats were carried out at intervals of 15, 30 and 90 min after intravenous administration of 14C-oxalate (37 MBq/kg BW). Hyperoxaluria was induced by vitamin B6 deficient diet. The procedure of macro and micro autoradiography is the same as that in normal rat., Results: In normal rats, macroautoradiogram showed that the radioactivity of 14C-oxalate exists in the whole kidney, and microautoradiogram identified this radioactivity mainly in the extraluminal space of renal tubules at 15 min. Macro and micro-autoradiograms taken 90 min after the injection showed practically no radioactivity of 14C-oxalate in the cortex or the medulla, but it was located in the extraluminal space of the papilla. In hyperoxaluric rats, macroautoradiogram showed some spotty accumulations of 14C-oxalate in the inner medulla and papilla. Microautoradiogram revealed that these accumulations are mainly seen in the extraluminal space., Conclusion: These results indicate that in normal rats the injected 14C-oxalate remains in the renal papilla, especially in the extraluminal space, when nearly all oxalate was excreted by urine, and in hyperoxaluric rats 14C-oxalate exists there as calcium oxalate crystal or microlith.

Objective: To study parameters which serve as criteria for differentiation of normal and abnormal uroflowmetrograms., Subjects and Methods: A total of 105 subjects were investigated, 43 of whom had no symptoms of dysuria, 57 of whom had dysuria demonstrated as an abnormal uroflowmetrogram, subjective symptoms and a small residual urine volume, and five patients who were about to undergo transurethral resection of the prostate. The three parameters used to specify the shapes of the uroflowmetrogram curves were: (i) the ratio of the maximum flow rate (Qmax) and the voiding time (T100), Qmax/T100; (ii) the ratio of the time to peak flow (TQmax) and the voiding time, TQmax/T100; and (iii) the newly introduced voiding efficiency (epsilon), measured by the ratio of the voided volume (VV) and T100 x Qmax, epsilon = VV/(T100 x Qmax), were taken for each patient., Results: The criteria for normal uroflowmetrograms were: Qmax/T100 > or = 0.78, 0.32 < or = TQmax/T100 < or = 0.54, 0.63 < or = epsilon < 1, respectively. In the patients who underwent transurethral resection of the prostate the values of all three parameters improved and returned almost to normal after operation., Conclusion: Using these three parameters the micturition pattern can be expressed quantitatively.

This is a case report of the 21st documented case of ureteral metastasis from renal cell carcinoma. A 75-year-old woman was admitted because of asymptomatic gross hematuria. Right radical nephrectomy for renal cell carcinoma had been performed 2 years and 9 months prior to admission. Cystoscopy revealed efflux of blood from right ureteral orifice. Right retrograde ureterogram revealed a filling defect at the upper end of the stump, where a soft tissue mass was observed by computerized tomographic scan. She underwent right ureteral stump excision with a bladder-cuff. Pathological study was consistent with metastatic renal cell carcinoma. The literature on ureteral metastasis from renal cell carcinoma is briefly reviewed and a mechanism for the metastasis is proposed.

Using a force plate and electromyographic recordings, changes in the muscle activity of the lower extremities during forward-inclining-posture walking and the free walking of healthy young adults were studied and compared with the free gait of healthy geriatrics. The movement of the hamstring, and the tibialis anterior and calf muscles caused a negative quadric curve during the forward-inclining gait and a positive curve during the free walking. However, the movements of the rectus femoris muscle caused a positive curve during the forward-inclining gait and a negative curve during the free walking. It also was found that geriatrics are thrown off balance by changes in cadence while walking. Further, greater muscular activity of the lower extremities is needed by geriatrics than by young adults during free walking, and the muscular movements of geriatrics during free walking showed no relation to the forward-inclining muscular movements of the young adults.

Two rare cases of urothelial tumor with high serum carcinoembryonic antigen (CEA) and TA-4 levels are presented. One is a case of lymph node metastasis due to bladder tumor: pathological diagnosis revealed mucoepidermoid carcinoma. The other is a case of left renal pelvic tumor: pathological diagnosis revealed transitional cell carcinoma with glandular and squamous differentiation. The serum CEA and TA-4 levels, high before surgery, decreased after surgery.

The pharmacokinetics of oxalate were studied in normal and nephrectomized rats with the use of radioisotope-labelled oxalate. The disappearance of [14C]oxalate from the plasma was analyzed with a two-compartment open model. The pharmacokinetic parameters of oxalate were compared with those for inulin. In normal rats, the plasma half-life of the elimination of oxalate was 0.33 +/- 0.06 h and that for inulin was 0.26 +/- 0.05 h (n = 10, mean +/- SD). The volume of distribution for oxalate was 56.7 +/- 6.80 and that for inulin 34.0 +/- 4.79 ml/100 g body weight, indicating that oxalate has access to additional compartments besides the extracellular volume. The total clearance of oxalate was 1.2 times higher than that for inulin. In nephrectomized rats, however, the plasma half-life of the elimination of oxalate was 1.85 +/- 0.34 h (n = 7, mean +/- SD) and that for inulin was 4.26 +/- 0.78 h. The total clearance of oxalate was 177 +/- 29 and that for inulin was 30 +/- 5 microliters/min/100 g body weight. In order to identify the extrarenal elimination route of oxalate, the bile of nephrectomized rats was collected. The hepatic clearance of oxalate was 31.2 +/- 2.7 microliters/min/100 g body weight. The biliary excretion of oxalate accounts for 17.6% of the total clearance in nephrectomized rats. Thus, other elimination processes of oxalate besides renal and hepatic clearance take place.

The antitumor activity of combination therapy of recombinant human tumor necrosis factor alpha (rHu-TNF alpha) and chemotherapeutic agents against murine bladder tumor (MBT-2) was studied. Tumors were intradermally transplanted into the hind leg of C3H-HeN mice and allowed to grow until they reached a diameter of 8 to 10 mm 10 days after transplantation. TNF (3,000 units) was given intraperitoneally from day 10 to day 19, and the chemotherapeutic agents, 5-FU (60 mg/kg), CPM (100 mg/kg), CDDP (10 mg/kg) and ADM (5 mg/kg), were applied once intraperitoneally on day 10. The antitumor effects were evaluated based on tumor volume on day 20. 5-FU, CPM and ADM enhanced the antitumor effect when combined with TNF, but CDDP did not. These findings suggest that combination therapy of TNF and certain antitumor chemotherapeutic agents is effective cancer treatment.