mTORC1 Controls Phase Separation and the Biophysical Properties of the Cytoplasm by Tuning Crowding.

Macromolecular crowding has a profound impact on reaction rates and the physical properties of the cell interior, but the mechanisms that regulate crowding are poorly understood. We developed genetically encoded multimeric nanoparticles (GEMs) to dissect these mechanisms. GEMs are homomultimeric scaffolds fused to a fluorescent protein that self-assemble into bright, stable particles of defined size and shape. By combining tracking of GEMs with genetic and pharmacological approaches, we discovered that the mTORC1 pathway can modulate the effective diffusion coefficient of particles ≥20 nm in diameter more than 2-fold by tuning ribosome concentration, without any discernable effect on the motion of molecules ≤5 nm. This change in ribosome concentration affected phase separation both in vitro and in vivo. Together, these results establish a role for mTORC1 in controlling both the mesoscale biophysical properties of the cytoplasm and biomolecular condensation.

Pilot dose-ranging of rhIGF-1/rhIGFBP-3 in a preterm lamb model of evolving bronchopulmonary dysplasia.

BACKGROUND: Low levels of insulin-like growth factor-1 (IGF-1) protein in preterm human infants are associated with bronchopulmonary dysplasia (BPD). We used our preterm lamb model of BPD to determine (1) dosage of recombinant human (rh) IGF-1 bound to binding protein-3 (IGFBP-3) to reach infant physiologic plasma levels; and (2) whether repletion of plasma IGF-1 improves pulmonary and cardiovascular outcomes. METHODS: Group 1: normal, unventilated lambs from 128 days gestation through postnatal age 5 months defined normal plasma levels of IGF-1. Group 2: continuous infusion of rhIGF-1/rhIGFBP-3 (0.5, 1.5, or 4.5 mg/kg/day; n = 2) for 3 days in mechanically ventilated (MV) preterm lambs determined that 1.5 mg/kg/day dosage attained physiologic plasma IGF-1 concentration of ~125 ng/mL, which was infused in four more MV preterm lambs. RESULTS: Group 1: plasma IGF-1 protein increased from ~75 ng/mL at 128 days gestation to ~220 ng/L at 5 months. Group 2: pilot study of the optimal dosage (1.5 mg/kg/day rhIGF-1/rhIGFBP-3) in six MV preterm lambs significantly improved some pulmonary and cardiovascular outcomes (p < 0.1) compared to six MV preterm controls. RhIGF-1/rhIGFBP-3 was not toxic to the liver, kidneys, or lungs. CONCLUSIONS: Three days of continuous iv infusion of rhIGF-1/rhIGFBP-3 at 1.5 mg/kg/day improved some pulmonary and cardiovascular outcomes without toxicity. IMPACT: Preterm birth is associated with rapid decreases in serum or plasma IGF-1 protein level. This decline adversely impacts the growth and development of the lung and cardiovascular system. For this pilot study, continuous infusion of optimal dosage of rhIGF-1/rhIGFBP-3 (1.5 mg/kg/day) to maintain physiologic plasma IGF-1 level of ~125 ng/mL during mechanical ventilation for 3 days statistically improved some structural and biochemical outcomes related to the alveolar formation that would favor improved gas exchange compared to vehicle-control. We conclude that 3 days of continuous iv infusion of rhIGF-1/rhIGFBP-3 improved some physiological, morphological, and biochemical outcomes, without toxicity, in mechanically ventilated preterm lambs.

Effects of glutamate positive modulators on cognitive deficits in schizophrenia: a systematic review and meta-analysis of double-blind randomized controlled trials.

Hypofunction of N-methyl-d-aspartate (NMDA) receptors has been proposed to have an important role in the cognitive impairments observed in schizophrenia. Although glutamate modulators may be effective in reversing such difficult-to-treat conditions, the results of individual studies thus far have been inconsistent. We conducted a systematic review and meta-analysis to examine whether glutamate positive modulators have beneficial effects on cognitive functions in patients with schizophrenia. A literature search was conducted to identify double-blind randomized placebo-controlled trials in schizophrenia or related disorders, using Embase, Medline, and PsycINFO (last search: February 2015). The effects of glutamate positive modulators on cognitive deficits were evaluated for overall cognitive function and eight cognitive domains by calculating standardized mean differences (SMDs) between active drugs and placebo added to antipsychotics. Seventeen studies (N=1391) were included. Glutamate positive modulators were not superior to placebo in terms of overall cognitive function (SMD=0.08, 95% confidence interval=-0.06 to 0.23) (11 studies, n=858) nor each of eight cognitive domains (SMDs=-0.03 to 0.11) (n=367-940) in this population. Subgroup analyses by diagnosis (schizophrenia only studies), concomitant antipsychotics, or pathway of drugs to enhance the glutamatergic neurotransmission (glycine allosteric site of NMDA receptors or α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors) suggested no procognitive effect of glutamate positive modulators. Further, no effect was found in individual compounds on cognition. In conclusion, glutamate positive modulators may not be effective in reversing overall cognitive impairments in patients with schizophrenia as adjunctive therapies.

Changes in antibiotic usage and susceptibility in nosocomial Enterobacteriaceae and Pseudomonas isolates following the introduction of ertapenem to hospital formulary.

There is concern that widespread usage of ertapenem may promote cross-resistance to other carbapenems. To analyse the impact that adding ertapenem to our hospital formulary had on usage of other broad-spectrum agents and on susceptibilities of nosocomial Enterobacteriaceae and Pseudomonas isolates, we performed interrupted time-series analyses to determine the change in linear trend in antibiotic usage and change in mean proportion and linear trend of susceptibility pre- (March 2004-June 2005) and post- (July 2005-December 2008) ertapenem introduction. Usage of piperacillin-tazobactam (P=0·0013) and ampicillin-sulbactam (P=0·035) declined post-ertapenem introduction. For Enterobacteriaceae, the mean proportion susceptible to ciprofloxacin (P=0·016) and piperacillin-tazobactam (P=0·038) increased, while the linear trend in susceptibility significantly increased for cefepime (P=0·012) but declined for ceftriaxone (P=0·0032). For Pseudomonas, the mean proportion susceptible to cefepime (P=0·011) and piperacillin-tazobactam (P=0·028) increased, as did the linear trend in susceptibility to ciprofloxacin (P=0·028). Notably, no significant changes in carbapenem susceptibility were observed.

Restoration of patency in iliofemoral deep vein thrombosis with catheter-directed thrombolysis does not always prevent post-thrombotic damage.

OBJECTIVES: To evaluate the long-term results of catheter-directed thrombolysis (CDT) and the feasibility of stent placement for lower extremity deep vein thrombosis (DVT). DESIGN & METHODS: Retrospective study of 34 patients (10 men and 24 women, mean age 55, S.D. 13 years) with lower extremity DVT underwent CDT at Seoul National University Hospital from January 1999 to October 2003. Patient characteristics, risk factors of DVT, extent of thrombosis, and short-term and long-term results of CDT and/or stent placement were analysed. RESULTS: Mean follow-up times were 47 S.D. 16 months. The primary technical success rate was 97% (complete lysis 68%, partial 29%). During the follow-up periods 11 (32%) patients showed re-thrombosis. Sixteen (47%) of 34 patients showed chronic change of vessels during the follow-up periods. By Cox Proportional Hazard analysis, extent of thrombolysis was a statistically significant factor affecting the freedom of re-thrombosis and chronic change (P=0.008 and P=0.001). Nine (44%) of 21 deployed stents were obstructed, and the overall stent patency at 3 years was 56.7%. The only factor affecting the stent patency was stent length more than 6 cm (P=0.002, HR 13, 95% CI 2.7-59). CONCLUSION: Long-term results of CDT are not satisfactory because of the high recurrence rate of DVT and it cannot prevent chronic post-thrombotic damage to the affected vessels despite long-term anticoagulation therapy. Careful long-term surveillance of the venous function is highly recommended after CDT.

Anorexiant-induced transient myopia after myopic laser in situ keratomileusis.

We report a case of acute transient myopia associated with ciliochoroidal effusion induced by anorexiants. The patient had had myopic laser in situ keratomileusis 7 years earlier. Acute bilateral myopia associated with anterior chamber shallowing, intraocular pressure elevation, diffuse ciliochoroidal effusion, and perimacular retinal folds was relieved 14 days after discontinuation of anorexiant medications. Tropicamide and atropine were used to deepen the anterior chamber. Sympathomimetic drugs such as phendimetrazine and ephedrine are used as anorexiants and may induce transient myopia associated with ciliochoroidal effusion, shallow anterior chamber, and acute angle-closure glaucoma.

Laser photocoagulation combined with intravitreal triamcinolone acetonide injection in proliferative diabetic retinopathy with macular edema.

PURPOSE: To evaluate therapeutic effects and usefulness of a combination treatment of intravitreal injection of triamcinolone acetonide (IVTA) and panretinal photocoagulation (PRP) in patients with clinically significant macular edema secondary to proliferative diabetic retinopathy (PDR). METHODS: Visual acuity test, fundoscopy, fluorescein angiography, and optical coherence tomography (OCT) were taken in 20 patients (20 eyes) of macular edema and PDR. A combination of intravitreal injection of triamcinolone acetonide and PRP was performed in 10 patients (10 eyes) and a combination of focal or grid laser photocoaqulation and PRP in the remaining 10 eyes. The postoperative outcomes were compared between the two combination treatments by best corrected visual acuity (BCVA), tonometry, fluorescein angiography, and OCT at 2 weeks, 1, 2, and 3 months. RESULTS: Average BCVA (log MAR) significantly improved from preoperative 0.56-/+0.20 to 0.43-/+0.08 at 1 month (P=0.042) and it was maintained until 3 months after a combination of IVTA and PRP in 10 eyes (P=0.007). The thickness of fovea decreased from average 433.3-/+114.9 micrometer to average 279.5-/+34.1 micrometer at 2 weeks after combined treatment of IVTA and PRP (P=0.005), which was significantly maintained until 3 months, but there was a transient visual disturbance and no significant difference in thickness of the fovea before and after treatment in the groups with PRP and focal or grid laser photocoagulation. CONCLUSIONS: A combination of IVTA and PRP might be an effective treatment modality in the treatment of macular edema and PDR and prevent the subsequent PRP-induced macular edema result in visual dysfunction. In combination with PRP, IVTA might be more effective than focal or grid laser photocoagulation and PRP for reducing diabetic macular edema and preventing aggravation of macular edema without transient visual disturbance in patients requiring immediate PRP.

Congenital sudoriferous cyst within the orbit followed by esotropia.

PURPOSE: To report a case of congenital sudoriferous cyst of the orbit with esotropia. METHODS: A 20-day-old male, born prematurely presented with a palpable lump on left upper lid. Orbital ultrasonography including color doppler image and orbital magnetic resonance image were performed to evaluate the lid lesion. The mass was excised and histologically examined. Complete ocular examination including visual acuity, duction, version, and the presence of strabismus were performed. RESULTS: A well circumscribed round cystic mass, measuring 1.4 x 1.3 cm was noted at medial superior aspect of the left orbit. It compressed and displaced the left globe to inferior posterior position with intact optic nerve. Histopathologic examination showed the lesion to be a solitary sudoriferous cyst lined by two layers of cuboidal epithelial cells with eosinophilic cytoplasm. After the excision of the mass, limitations of extraocular muscle movements, esotropia, and amblyopia were noted. CONCLUSIONS: If an orbital cyst affects the globe or extraocular muscles, it should be excised as soon as possible to prevent strabismus and amblyopia especially in infant.

Artisan phakic intraocular lens implantation after retinal detachment surgery.

PURPOSE: To report three cases of Artisan phakic intraocular lens (PIOL) implantation to correct myopic refractive error after previous retinal detachment surgery treated with scleral encircling. METHODS: Artisan PIOLs were implanted in a 29-year-old man with -21.0 -2.0 x 180 manifest refraction and best spectacle-corrected visual acuity (BSCVA) of 20/40 (case 1), a 28-year-old woman with BSCVA of 20/20 and -8.5 -1.0 x 180 manifest refraction (case 2), and a 44-year-old man with BSCVA of 20/32 and -11.75 -1.75 x 10 manifest refraction (case 3). RESULTS: In case 1, 24 months after implantation of the Artisan PIOL, uncorrected visual acuity (UCVA) was 20/40. In case 2, 24 months after surgery, UCVA was 20/32. In case 3, 3 months after surgery, UCVA was 20/32. There was no formation of new breaks, progressive vitreoretinal traction, or complications. CONCLUSIONS: The Artisan PIOL may provide an alternative method to correct high myopia after retinal detachment surgery.

FDG uptake and glucose transporter type 1 expression in lymph nodes of non-small cell lung cancer.

AIMS: FDG uptake in NSCLC is related to glucose transporter type 1 (Glut-1) expression. Here, we investigated the direct causal relationship between FDG uptake and Glut-1 expression to determine the role of Glut-1 in FDG uptake by malignant and benign lymph nodes (LNs). METHODS: Fifty-five curative lung resections in 53 NSCLC patients (male:female=36:17, age=62.0+/-11.8 years) were included. Maximum standardized uptake values (maxSUVs) of LNs in preoperative whole body FDG-PET and Glut-1 immunostaining results were compared. RESULTS: Of 316 pathologically confirmed LNs, 12.3% (39/316) were malignant, and in malignant LNs, FDG positive LNs were no different from FDG negative LNs in terms of size (15.0+/-6.7 mm vs 10.0+/-6.1mm, p>0.05), or in terms of the proportion of LNs occupied by tumor (60.0+/-28.8% vs 39.2+/-38.4%, p>0.05), but had greater percentages of Glut-1 positive cells in tumors (74.1+/-31.8% vs 22.7+/-18.7%, p<0.01), and Glut-1 staining intensities (3.4+/-0.9 vs 1.8+/-1.3, p<0.01). FDG negative malignant LNs featured cytoplasmic Glut-1 expression and adenocarcinoma. Glut-1 staining intensities were found to be significantly correlated with the maxSUVs of malignant LNs (rho=0.516, p<0.05), but the percentages of Glut-1 positive cells in tumors were not (r=0.2072, p>0.05). Analysis of FDG positive benign LNs showed that maxSUV was not correlated with degree of follicular hyperplasia, or Glut-1 expression (p>0.05). CONCLUSIONS: Intense Glut-1 immunoreactivity was found to be proportionally related to the degree of FDG uptake by malignant LNs in NSCLC. However, the finding that Glut-1 expression in lymphoid hyperplasia showed no correlation with FDG uptake in benign LNs requires further investigation.

Detection of response-predicting mutations in the kinase domain of the epidermal growth factor receptor gene in cholangiocarcinomas.

PURPOSE: Epidermal growth factor receptor (EGFR) signalings have recently been implicated in the genesis and progression of cholangiocarcinomas. Thus, the EGFR kinase inhibitor appears to be promising in the treatment of this cancer. The response-predicting mutations in the tyrosine kinase domain of EGFR gene have recently been detected in non-small cell lung cancers. This study was, therefore, to investigate if these mutations are also found in cholangiocarcinomas. METHODS: Twenty-two consecutive cholangiocarcinoma patients who underwent surgical resection were enrolled. Their resected paraffin-embedded cholangiocarcinoma specimens were used for mutation analysis, which was performed by DNA sequencing of exons 18, 19 and 21 in the EGFR gene. Clinical characteristics were compared between each group according to the presence or absence of mutations. RESULTS: Three patients (13.6%) harbored EGFR mutations. All the mutations found were deletions in exon 19. Mutations were more common in intra-hepatic or poorly differentiated tumors. Differences in age, sex, stage at diagnosis and survival were not observed between mutation-positive and -negative patients. CONCLUSIONS: This study, for the first time, demonstrates that a subset of cholangiocarcinoma patients has response-predicting EGFR mutations. Therefore, a highly selected application of the EGFR kinase inhibitor would be therapeutically effective in these patients.

A cell surface molecule, JL1; a specific target for diagnosis and treatment of leukemias.

We previously reported a novel differentiation antigen, which is specifically expressed in stage II double positive (CD4+CD8+) human cortical thymocytes (Park et al, J Exp Med 1993; 178: 1447-1451). This study was designed to investigate the expression pattern of JL1 in various types of leukemic cells from patients and normal hematopoietic cells to evaluate the possibility as a tool for diagnosis and treatment of leukemia. The expression of JL1 antigen was observed in 75.6% of leukemic cases (117 out of 154 leukemic patients tested) on flow cytometric analysis. The percentage of JL1-positive cases of T lineage acute lymphoblastic leukemia (T-ALL) (92.6%) was higher than that of other types of leukemias (75%). The presence of JL1 antigen was also confirmed by immunoblotting and immunoprecipitation. Since the JL1 antigen is selectively expressed on the surface of human leukemic cells but not on the mature human peripheral blood cells, normal bone marrow cells and various types of normal tissues, JL1 could be an excellent candidate for an immunodiagnostic and immunotherapeutic tool for hematopoietic malignancies such as leukemia.

Parametric image of myocardial blood flow generated from dynamic H2(15)O PET using factor analysis and cluster analysis.

Algorithm-based parametric imaging of myocardial blood flow (MBF), as measured by H2(15)O PET, has been the goal of many research efforts. A method for generating parametric images of regional MBF by factor and cluster analysis on H2(15)O dynamic myocardial PET was validated by its comparison with gold-standard MBF values determined invasively using radiolabelled microspheres. Right and left ventricular blood pool activities and their factor images were obtained by the application of factor analysis to dynamic frames. By subtraction of the factor images multiplied by their corresponding values on the factors from the original dynamic images for each frame, pure tissue dynamic images were obtained, from which arterial blood activities were excluded. Cluster analysis that averaged pixels having time-activity curves with the same shape was applied to pure tissue images to generate parametric MBF images. The usefulness of this method for quantifying regional MBF was evaluated using canine experiment data. H2(15)O PET scans and microsphere studies were performed on seven dogs at rest and after pharmacological stress. The image qualities and the contrast of parametric images obtained using the proposed method were significantly improved over either the tissue factor images or the parametric images obtained using a conventional method. Regional MBFs obtained using the proposed method correlated well with those obtained by the region of interest method (r = 0.94) and by the microsphere technique (r = 0.90). A non-invasive method is presented for generating parametric images of MBF from H2(15)O PET, using factor and cluster analysis.

Hypoglycemia-induced cerebellar dysfunction and quantitative positron emission tomography study.

OBJECTIVE: To describe an unusual case of hypoglycemia-induced bilateral cerebellar dysfunction. BACKGROUND: The cerebellum is known to be resistant to hypoglycemia, and selective cerebellar dysfunction caused by hypoglycemia has not been reported. Previous studies showed that the ratio between the rate constants for glucose uptake and phosphorylation (K1 and k3) is reversed in the cerebellum compared with the cerebral cortex; higher K1 in the cerebellum and higher k3 in the cerebral cortex. METHODS: Quantitative dynamic PET scanning with labeled fluorodeoxyglucose (18F-FDG) was performed to prove altered glucose kinetics in the cerebellum of a patient who presented with episodic cerebellar dysfunction associated with hypoglycemia. Four control subjects underwent the same study. RESULTS: The ratio between K1 and k3 was not reversed in the cerebellum of our patient (K1 = 0.082, k3 = 0.192). On the contrary, the ratio was reversed in the control subjects (mean K1 = 0.109, mean k3 = 0.080). In addition, the patient's cerebellar metabolic rate of glucose (rCMRglu = 27.9 micromol/100 g/minute) and the rate constant of glucose egress (k2 = 0.543) were relatively increased compared with those of control subjects (mean rCMRglu = 21.9 micromol/100 g/minute, mean k2 = 0.352). CONCLUSIONS: In a case of episodic bilateral cerebellar dysfunction caused by hypoglycemia, quantitative dynamic PET study demonstrated decreased glucose uptake-to-utilization ratio and increased leak of glucose in the cerebellum. The cerebellum is not invariably resistant to hypoglycemia.

Tumor concentration and distribution of carcinoembryonic antigen measured by in vitro quantitative autoradiography.

UNLABELLED: One of the most critical factors in successful immunoscintigraphy and radioimmunotherapy is the local concentration and distribution of the target antigen. The purpose of this study was to evaluate the concentration and distribution of carcinoembryonic antigen (CEA) in various carcinomas. METHODS: In vitro quantitative autoradiography was performed in carcinomas of the stomach (32 cases), colon (20 cases), breast (29 cases) and lung (26 cases). Frozen tumor sections were incubated with varying concentrations of 125I-labeled monoclonal antibody (Mab) CEA-79.1 (IgG2a), which is specific for CEA. Digitized autoradiographic images from these sections were compared to adjacent H & E and immunoperoxidase-stained sections. Computer analysis of specific antibody binding quantitated the maximal value (Bmax), which is equal to the concentrations of CEA. RESULTS: Stomach cancer expressed CEA in 31 cases (97%). All colon cancer specimens exhibited CEA and breast cancer expressed CEA in 24 cases (83%). In adenocarcinoma of the lung, CEA was measured in all specimens. The concentration of CEA did not vary significantly among the pathologic types or among the various degrees of differentiation in each carcinoma. CEA was expressed homogeneously in adenocarcinomas of the colon and lung. However, CEA exhibited a heterogeneous distribution in a significant number of breast cancer (42%) and bronchogenic squamous-cell carcinoma (78%) specimens. CONCLUSIONS: CEA was expressed in most cases of stomach, colon, breast and lung carcinomas. These carcinomas, however, exhibited wide variation in the concentration and distribution of CEA expression. The concentration and distribution of CEA in a particular tumor type should be considered before undertaking tumor targeting methods.

Transient prolonged stunning induced by dipyridamole and shown on 1- and 24-hour poststress 99mTc-MIBI gated SPECT.

UNLABELLED: We investigated whether poststress gated SPECT, which was believed to show resting wall motion, revealed stunning induced by dipyridamole stress. METHODS: In 62 patients with coronary artery disease (n = 57) or chest pain (n = 5), dipyridamole stress gated 99mTc-hexakis-2-methoxyisobutyl isonitrile (MIBI) SPECT and rest 201Tl SPECT were performed on the first day; 24-h delayed 201Tl SPECT and rest gated 99mTc-MIBI SPECT were performed on the second day. Stress and rest gated 99mTc-MIBI SPECT was performed 1 h after injection. The myocardium was divided into 17 segments, and perfusion was scored on a 4-point scoring system (scores, 0-3 for normal to defect); wall motion during first-day poststress gated and second-day rest gated SPECT was also scored on another 4-point scale (scores, 0-3 for normal to dyskinesia). RESULTS: Thirty-one of 62 patients showed wall motion abnormality that was worse after stress than during resting. Three hundred eight (29%) of the total 1054 segments showed wall motion abnormality on poststress gated SPECT. In 198 of these segments, wall motion abnormality was the same on poststress and rest gated SPECT, and 106 segments showed wall motion that was worse on 1-h poststress than on rest gated SPECT. Perfusion was normal either during rest (n = 113) or after a 24-h delay (n = 18) in 131 segments with the poststress wall motion abnormality. Of these 131 segments, 69 showed the same wall motion abnormality between poststress and resting periods (persistent stunning). However, in 40 segments, abnormal wall motion on 1-h poststress gated SPECT normalized on rest gated SPECT (transient prolonged stunning). The other 20 segments showed improvement of wall motion during rest compared with the poststress period but still showed abnormal wall motion during the resting period (between transient prolonged stunning and persistent stunning). Stress perfusion decrease was more severe in transient prolonged stunning than in persistent stunning. Poststress wall motion abnormality was more severe in persistent stunning. CONCLUSION: Using gated 99mTc-MIBI SPECT, stunned myocardium was found on 1-h poststress SPECT compared with normal resting wall motion found on rest gated SPECT on the next day. We conclude that some myocardial walls did not show true resting wall motion on 1-h poststress gated SPECT; hence, caution is necessary when using wall motion on 1-h poststress gated SPECT to assess resting wall motion.

Bone marrow scintigraphy using technetium-99m-antigranulocyte antibody in hematologic disorders.

UNLABELLED: Bone marrow is the primary site for many hematologic disorders. To date, however, no suitable bone marrow imaging method has been found. The present study investigates the usefulness of bone marrow immunoscintigraphy using 99mTc-labeled antigranulocyte antibody (anti-NCA-95) in 31 patients with hematologic disorders. METHODS: One milligram of antibody labeled with 259-370 MBq 99mTc was injected intravenously, and bone marrow images were taken 4 hr later. We also calculated the uptake ratios of lumbar bone marrow-to-background (L/B) and ilium-to-background (I/B). RESULTS: Of 15 patients with aplastic anemia, 7 showed diffusely decreased antibody uptake (L/B = 2.3 +/- 0.8, I/B = 3.0 +/- 0.8) compared to control patients (n = 21, L/B = 8.2 +/- 2.5, I/B = 10.3 +/- 3.1) Six patients had both decreased and increased uptake areas and two had normal to slightly increased uptake. Of those patients receiving various types of therapy for aplastic anemia, all but one showed increased or irregular uptake. The degree of antibody uptake in the bone marrow correlated with peripheral blood analyses (hemoglobin, white blood cells, platelets). Of six patients with myelodysplastic syndrome, four had irregular uptake and two diffusely decreased uptake. Four patients with myelogenous leukemia showed normal uptake, whereas two with lymphocytic leukemia had decreased uptake. Patients with iron deficiency anemia, pure red cell aplasia or thalassemia minor exhibited normal uptake with bone marrow expansion. CONCLUSION: Immunoscintigraphy with antigranulocyte antibody is a useful method for evaluating the bone marrow status of patients with various hematologic disorders.

Clinical immunoscintigraphy of ovarian carcinoma using iodine-131-labeled 145-9 monoclonal antibody.

The monoclonal antibody (Mab) designated 145-9 recognizes CA125 antigen but binds to a different epitope than that recognized by OC125 antibody. This is a clinical study assessing the safety, kinetics and imaging sensitivity of Mab 145-9. Two milligrams of Mab were labeled with 111 MBq (3.0 mCi) of 131I and infused intravenously in 18 patients with ovarian carcinoma. Immunoscintigraphies were done at three, five, and seven days. There were no adverse reactions to the injection of this Mab. All immunoscintigraphies were considered positive. Immunoscintigraphy detected tumor lesions were confirmed in operative fields, in two patients with normal serum levels of CA125 and in four patients whose sonography and/or x-ray computed tomography showed negative findings. In five patients, immunoscintigraphy was repeated without any adverse reaction and revealed the progress of the carcinoma. Pharmacokinetic studies showed the steady-state volume of distribution (Vdss) to be 2772 +/- 466 ml (mean +/- s.d.), and clearance 51.3 +/- 12.7 ml/hr. In summary, immunoscintigraphies using 131I-labeled Mab 145-9 were done safely in patients with ovarian carcinoma. Preliminary results reveal a high sensitivity compared to radiological methods and tests currently in use.

Clinical significance of hepatic visualization on iodine-131 whole-body scan in patients with thyroid carcinoma.

UNLABELLED: The purpose of this study was to evaluate the frequency and clinical significance of diffuse hepatic uptake on 131I whole-body scan in 399 patients (53 males, 348 females) with well-differentiated adenocarcinomas of the thyroid. METHODS: Two hundred and ninety-one diagnostic scans were performed 2 days after the administration of 74-370 MBq (2-10 mCI) 131I, and 824 post-therapy scans were done 3-5 days after the administration of 1.11-7.4 GBq (30-200 mCI) 131I. There was no evidence of liver metastasis in these patients. Liver and thyroid visualization on each 131I scan were graded from 0-4. To evaluate the incorporation of radioiodine to thyroglobulin and thyroid hormones, a patient's serum was extracted by 80% ethanol/20% trichloroacetic acid solution and analyzed by silica gel thin-layer chromatography. RESULTS: Diffuse hepatic uptake (> Grade 2) was definitely seen in 239 of 399 (59.9%) of the patients and 397 of 1115 (35.6%) of the studies. In the diagnostic scans, 36 (12.0%) showed uptake in the liver. In post-therapy scans, however, the incidence of liver uptake increased according to increased doses of 131I (39.1% with 1.11 GBq, 61.5% with 2.775-3.7 GBq and 71.3% with 5.55-7.4 GBq). The more that uptake appeared in the residual thyroid, the more it appeared in the liver. There were 13 patients whose scans showed metastatic and liver uptake without any thyroid uptake. Fifteen patients showed diffuse liver uptake without uptake by the thyroid or metastasis. Follow-up studies of seven of these patients revealed metastatic lesions. Liver uptake on scan related to the fraction of 131I-labeled thyroglobulin in the serum. CONCLUSION: Diffuse liver uptake indicated functioning thyroid remnant or metastasis. In a few cases, liver uptake without uptake by the thyroid or metastasis on whole-body scans suggests hidden metastases.

Crossed-cerebellar diaschisis in cerebral infarction: technetium-99m-HMPAO SPECT and MRI.

UNLABELLED: We studied 26 patients with a single supratentorial infarction using 99mTc-HMPAO SPECT and MRI to investigate the phenomenon of crossed-cerebellar diaschisis (CCD). METHODS: From the total single-photon emission counts obtained from each cerebellar hemisphere, the percent difference between the contralateral (CCH) and ipsilateral (ICH) cerebellar hemispheres [delta %cbll = (CCH-ICH)/ ICH x 100] was calculated. Both SPECT (SVD) and MRI volume deficit (MVD) were measured to examine their relationship with CCD. RESULTS: A CCD was observed in 12 of the 26 patients (46%) with cerebral infarction. There was no significant correlation between SVD and delta %cbll or MVD and delta %cbll in the patients with cerebral infarction. There were no significant differences in SVD and MVD between the patients with and without CCD. The frequency of CCD was significantly higher in the patients whose infarctions were in the frontoparietal lobes or the deep middle cerebral artery territory, including the basal ganglia and internal capsule (11/19) than in the patients whose infarctions were in other regions (1/7) (p = 0.048). The severely hemiparetic patients had a higher frequency of CCD and lower delta %cbll than the patients with milder or no hemiparesis (frequency, 5/5 compared with 6/18, p = 0.008; delta %cbll, -21.4% +/- 3.8% compared with -8.3% +/- 11.1%, p = 0.018). However, CCD also occurred in 5 of the 14 patients without hemiparesis and was not seen in 5 of the 12 hemiparetic patients. None of the patients with CCD demonstrated the apparent clinical signs of cerebellar dysfunction. CONCLUSION: The location rather than the extent and severity of the lesion may be the major determinant for the occurrence and magnitude of CCD in patients with cerebral infarction. Our results also support the notion that CCD is a consequence of the interruption of the corticopontocerebellar pathway at the supratentorial level.