Monitoring of methylergometrine in human breast milk by solid-phase extraction and high-performance liquid chromatography with fluorimetric detection.

A high-performance liquid chromatographic assay has been developed for the detection and quantification of the conventional postnatal uterotonic drug, methylergometrine, in human breast milk using a C-18 reversed-phase column by isocratic elution. The analytical method consisted of sample clean-up by solid-phase extraction, and the fluorescence detection required only 8.5 min per sample for separation and quantitation. This assay gave intra- and inter-assay coefficients of variation of less than 7.9% and 7.7%, respectively, and the detection limit was approximately 50 pg/ml. This method was applied for drug level monitoring in the breast milk of patients given methylergometrine.

[Ruptured aortic arch aneurysm with hemorrhagic cardiac tamponade; report of a case].

We report a case of successful treatment of a ruptured distal aortic arch aneurysm with cardiac tamponade by using selective cerebral perfusion for protecting the brain. A 79-year-old man had sudden onset of severe chest and back pain. Chest computed tomography (CT) suggested an acute aortic dissection. He was immediately transferred to the emergency room of our hospital. Echocardiography performed on admission revealed intrapericardial fluid, and hemodynamic monitoring suggested cardiac tamponade. After pericardiocentesis and removal of 400 ml bloody fluid, his hemodynamic condition became stable. Enhanced chest CT showed ruptured distal aortic arch aneurysm with pericardial and pleural effusion. Emergency patch plasty of the aneurysm under extracorporeal circulation (ECC) was performed, assisted by selective cerebral perfusion and deep hypothermia. The patient's postoperative course was uneventful, except for minor transient respiratory troubles, and he was able return to his usual activity.

Clinical outcome after CyberKnife® radiosurgery re-irradiation for recurrent brain metastases.

PURPOSE: The objective of this study was to elucidate the impact on clinical outcomes resulting from re-irradiation for locally recurrent (LR) brain metastases (BM) using CyberKnife® stereotactic radiosurgery (SRS). MATERIALS AND METHODS: Seventy-seven patients with 254 LR BM lesions treated using SRS re-irradiation between January 2014 and December 2018 were analysed in this retrospective study. The local control (LC), overall survival (OS) rates, and adverse events were assessed. The adverse events were classified according to the Common terminology for adverse event (CTCAE) v5.0. RESULTS: The median follow-up duration was 8.9 months. The median age of the patients was 55 years (IQR: 47-62). The 3, 6, and 9-month LC and OS rates were 92.2%, 73.4%, and 73.4% and 79.2%, 61.0%, and 48.1%, respectively. On multivariate analysis the gender (male vs. female; HR, 1.79; 95% CI, 1.06-3.01; P=0.028), type of first brain radiation (WBI vs. SRS) followed by re-irradiation using SRS (HR, 9.32; 95% CI, 2.77-15.27; P<0.001) tumour volume (>12cc vs. ≤12cc; HR, 1.84; 95% CI, 1.10-3.11; P=0.02), and recursive partitioning analysis (RPA) (I vs. II & III; HR, 0.38; 95% CI, 0.19-0.70; P=0.001) were independent predictive factor for OS. Radionecrosis was reported in 3 patients. CONCLUSION: With acceptable toxicity, SRS re-irradiation for LR BM showed a favourable rate for LC and OS and reported better OS for the female gender, a patient undergoing first brain radiation with SRS, tumour volume ≤12cc, and RPA-I. This result needs to be further evaluated in future clinical studies.

Involvement of the protein kinase Cgamma isoform in development of tolerance to nitrous oxide-induced antinociception in mice.

Prolonged exposure to nitrous oxide (N2O) results in development of acute tolerance to its antinociceptive effect. Cross-tolerance to N2O-induced antinociception is also observed in morphine-tolerant animals. Despite increasing evidence of tolerance development to N2O-induced antinociception, the details of the mechanisms that underlie this tolerance remain unknown. The present study was conducted to investigate the involvement of brain protein kinase C (PKC) isoform in these two types of tolerance to N2O-induced antinociception in mice. Prolonged exposure (41 min in total, including 30 min pre-exposure and 11 min of antinociceptive testing) to 70% N2O produced a reduction in N2O-induced antinociception, indicating development of acute tolerance. The prolonged exposure to 70% N2O caused an activation of PKCgamma isoform in the brain, but not the PKCepsilon isoform. Pretreatment with a PKCgamma-antisense oligonucleotide but not the corresponding mismatch oligonucleotide (i.c.v.) prevented the development of acute tolerance to N2O-induced antinociception. Chronic morphine treatment (10 mg/kg, s.c., b.i.d. for 5 days) resulted in development of tolerance to morphine-induced antinociception and cross-tolerance to N2O-induced antinociception. The development of tolerance to morphine and cross-tolerance to N2O were both inhibited by pretreatment with PKC inhibitor, chelerythrine (1 nmol, i.c.v.). Morphine-tolerant mice showed an activation of PKC within the brain, which was suppressed by pretreatment with chelerythrine (1 nmol, i.c.v.). Thus, activation of brain PKC, in particular, the PKCgamma isoform, appears to play an important role in the development of both acute tolerance and cross-tolerance to N2O-induced antinociception in mice.

[Ventricular septal perforation due to weak blunt chest trauma; report of a case].

We report a 67-year-old female patient with ventricular septal perforation after weak blunt chest trauma. She tumbled down on a frozen street. Approximately 1 week later, the patient was aware of shortness of breath on exertion. On admission, holosystolic murmur was detected on chest wall and routine electrocardiogram examination showed ST-T change which suggested myocardial ischemia. Acute myocardial infarction and ventricular septal defect with left-to-right shunt was suspected. The echocardiography and cardiac catheterization revealed the muscular type ventricular septal perforation near the apex with large left-to-right shunt flow (82% shunt ratio). The congestive heart failure was controlled successfully by conservative medical treatment. Surgical repair was scheduled on the 28th day after initial chest trauma because of large left-to-right shunt. A hole of about a diameter of 2 cm with fibrous edge of the muscular septum was closed through a left ventriculotomy using a Dacron patch under cardiopulmonary bypass. Postoperative course was uneventful and the patient was discharged without symptoms of congestive heart failure.

Distribution of ASIC4 transcripts in the adult wild-type mouse brain.

Acid-sensing ion channel 4 (ASIC4) belongs to the ASIC gene family of neuronal proton-gated cation channels, and is the least understood subtype among the members. Previous studies of ASIC4 expression in the mammalian central nervous system have shown that ASIC4 is abundantly expressed in the spinal cord and in various brain regions, such as the cerebral cortex, the hippocampus, and the cerebellum. However, the detailed distribution of ASIC4 transcripts in mammalian brains still remains to be elucidated. In the present study, radioactive in situ hybridization histochemistry with an ASIC4-specific cRNA probe was performed on wild-type mouse brains, followed by X-gal staining experiments with Asic4-lacZ reporter mice Asic4tm1a(KOMP)Mbp. It was found that ASIC4 mRNAs were widely expressed throughout the wild-type brain, but preferentially concentrated in the olfactory bulb, the piriform cortex, the caudate putamen, the preoptic area, the paraventricular nucleus, the medial habenular nucleus, the pretectal area, the lateral geniculate nucleus, the amygdaloid complex, the superior colliculus, the interpeduncular nucleus, and the granule cell layer of the ventral hippocampus, and these results were in agreement with the X-gal-positive reactions observed in the mutant brain. In addition, X-gal staining combined with immunohistochemistry identified intense signals for ASIC4 transcriptional activity in most of the choline acetyltransferase (ChAT)-positive principal neurons located in the basal forebrain cholinergic nuclei. Our data provide useful information to speculate possible roles of ASIC4 in diverse brain functions.

Antitumor effect of actinomycin D entrapped in liposomes bearing subunits of tumor-specific monoclonal immunoglobulin M antibody.

Sonicated liposomes containing actinomycin D in the membranes were chemically coated with the subunits of monoclonal immunoglobulin M (IgM) antibody against a mouse mammary tumor-associated antigen (MM antigen) and examined for their in vitro and in vivo antitumor effects against MM46 (MM+) and MM48 (MM-) tumors of C3H/He mouse origin. The antibody-bearing, actinomycin D-containing liposomes (chemoimmunoliposomes) were selectively bound to MM+ tumor cells and showed much more in vitro cytotoxicity against the tumor cells than that shown by free actinomycin D. The in vivo antitumor effect of the chemoimmunoliposomes was tested on the mammary tumor cells (5 X 10(4) to 5 X 10(6) transplanted i.p. into syngeneic mice. A single i.p. injection of the chemoimmunoliposomes containing 0.3, 0.5, or 1 microgram of actinomycin D into MM46 tumor-bearing mice resulted in the cure of some mice and a prolonged survival time in the rest of the mice as compared to results in controls. In this test, free actinomycin D, anti-MM IgM antibody, and bovine serum albumin-coated liposomes containing actinomycin D were marginally effective or ineffective. To examine a systemic antitumor effect of chemoimmunoliposomes, mice were inoculated with MM46 tumor cells and then treated with a single i.v. injection of liposomes 4 days later. If the mice were pretreated with an i.v. injection of unmodified multilamellar liposomes, an injection of the chemoimmunoliposomes containing 1 microgram of actinomycin D resulted in a significant inhibition of tumor growth. Both free actinomycin D and bovine serum albumin-coated liposomes containing actinomycin D were ineffective against the s.c. tumor. These results indicate that an antitumor drug entrapped in the membranes of small sonicated liposomes bearing antitumor monoclonal antibodies can be delivered to antigenic tumor cells and exert more efficient antitumor activity than does the free drug.

Frequent beta-catenin mutation and cytoplasmic/nuclear accumulation in pancreatic solid-pseudopapillary neoplasm.

Significance of Wnt signaling with beta-catenin mutations on solid-pseudopapillary neoplasm (SPN) of the pancreas was studied by immunohistochemistry and molecular analysis. On immunohistochemistry, all 18 SPNs tested showed diffuse cytoplasmic/nuclear positivity for beta-catenin. Upon direct DNA sequencing of exon 3 of the beta-catenin gene, 15 (83%) of the 18 SPNs showed 1-bp missense mutation in codons 32 (5 cases), 33 (3 cases), 34 (3 cases), 37 (3 cases), and 41 (1 case). Immunoreactivity for cyclin D1, one of the intranuclear targets of beta-catenin complexes, was found in tumor cells of more than half the tumor cells of all of the 18 SPNs. The present study strongly suggested a significant role of Wnt signaling, mostly associated with beta-catenin mutations in the tumorigenesis of SPN.

Neuropathic Pain Features in Patients with Bone Metastases.

AIMS: The results of previous randomised controlled trials suggest that radiation oncologists should consider the presence of neuropathic pain when they prescribe dose fractionations for painful bone metastases. Although validated screening tools for neuropathic pain features are currently available, the prevalence of such features among patients with painful bone metastases is still poorly understood. The purpose of this study was to estimate the prevalence of neuropathic pain features among patients who received palliative radiotherapy for painful bone metastases. MATERIALS AND METHODS: We conducted a cohort survey of consecutive patients who received palliative radiotherapy for painful bone metastases at St Luke's International Hospital between 2013 and 2014. Patients were prospectively assessed before radiotherapy using the validated screening questionnaire to identify neuropathic pain components in Japanese patients. Pain with neuropathic features was prospectively defined using the total score of the seven-item questionnaire and a cut-off score ≥9. The pain response was assessed 2 months after the start of radiotherapy according to the criteria defined by the International Bone Metastases Consensus Working Party. RESULTS: Eighty-seven patients were assessed. Twenty-four per cent of patients (95% confidence interval: 16-35%) were diagnosed as having pain with neuropathic features. On multivariate analysis, no significant correlations were seen between neuropathic pain features and patient characteristics. Sixty-four patients (74%) were assessable 2 months after the start of radiotherapy. Overall response rates were 59% (95% confidence interval: 33-82%) in patients with neuropathic features and 55% (95% confidence interval: 40-70%) in those without such features. CONCLUSIONS: A considerable proportion of the patients were proven to have bone pain with neuropathic features. Further investigations are warranted to validate symptom assessment tools in cooperation with pain distribution and image findings, and to clarify if the presence of neuropathic pain affects the response to palliative radiotherapy.

Rossette formation between stromal and hemopoietic cells: a simple assay for the supportive activity of stromal cells.

Hemopoietic stromal cells play an important role in the proliferation and differentiation of hemopoietic cells in vitro. Recently, it has been emphasized that the attachment of hemopoietic cells to stromal cells is the first step in this process and that this is necessary in hemopoiesis in vitro. A rosette formation technique was developed to quantitatively measure this attachment. The murine leukemic cell line ELM-D, which grows only in close contact with stromal cells, was used to represent hemopoietic cells. Rosettes were formed with about 75% of the normal murine bone marrow derived hemopoietic supportive stromal cells (MS-1). However, ELM-D formed rosettes with only 15% of the hemopoietic non-supportive stromal cells (MS-K). The maximum rosette formation was obtained at an ELM-D to MS-1 ratio of 20:1. When MS-1 and MS-K were mixed and seeded as stromal cells, MS-K did not alter the attachments of ELM-D to MS-1; the percentage of rosette formation increased in parallel with the increase in the number of MS-1 cells in the stromal layer. These findings suggest that MS-K does not have an inhibitory effect. Rosette formation is a simple, quantitative technique for assaying the hemopoietic supportive activity of stromal cells in vitro.

Treatment of Philadelphia chromosome-positive acute lymphoblastic leukemia: a pilot study which raises important questions.

Acute lymphoblastic leukemia (ALL) patients with a Philadelphia chromosome (Ph+ ALL) were treated with a combination of antineoplastic drugs recommended for both myeloid and lymphoid leukemia (BHAC-DMPV: behenoylcytosine arabinoside, daunorubicin, 6-mercaptopurine, prednisolone, and vincristine). Ph+ ALL patients with chromosome breaks which occur within the major breakpoint cluster region (M-BCR rearranged Ph+ ALL) were treated with natural interferon-alpha (IFN-alpha) after entering complete remission. In this study, four of seven patients with Ph+ ALL had M-BCR rearrangement, and all achieved complete remission with karyotypic normalization. Subsequent cytogenetic analysis during complete remission in two ALL patients with M-BCR rearrangement revealed that the percentage of bone marrow cells with the Ph chromosome increased, while the bone marrow maintained remission status. This cytogenetic-hematological discrepancy led us to consider that M-BCR rearranged Ph+ ALL might be a variant of chronic myelogenous leukemia, therefore, three Ph+ ALL patients with M-BCR rearrangement were treated with IFN-alpha after achieving complete remission. In contrast, only one of three patients with M-BCR non-rearranged Ph+ ALL obtained complete remission.

Monoclonal antibodies against human follicle-stimulating hormone.

Five monoclonal antibodies to human (h) FSH have been prepared, isolated, and characterized. They were produced by hybridomas derived from FO myeloma cells and spleen cells from mice immunized with hFSH or its beta-subunit (hFSH beta). Two of the antibodies (A101 and A102) which recognized the alpha-subunit of hFSH bound much better when alpha was associated with the beta-subunit forming the intact hFSH molecule than when alpha was in free form. These antibodies showed 9-10%, 2-3%, and 1-3% cross-reactions with alpha-subunits in hTSH, hCG, and hLH, respectively. Two antibodies (B201 and B202) recognized only free beta-subunit. One antibody (B305) recognized free beta-subunit and native hFSH. There was no significant cross-reaction of these antibodies to FSH beta with hTSH, hLH, and hCG. Using solid phase competitive binding and sandwich assays, we compared the epitopes for these antibodies. Antibodies A101 and A102 recognize the same epitope on hFSH alpha. Antibodies B201 and B202 recognize different epitopes, but they seemed to be adjacent. Antibody B305 bound a different epitope than B201 and B202. Such characteristics of these antibodies can be useful for sensitive and specific assay of hFSH or hFSH beta and also may be helpful in studying FSH interaction with its receptor.

The antigenic structure of the human glycoprotein hormone alpha-subunit. I. Characterization of anti-alpha monoclonal antibodies.

The glycoprotein hormones CG, LH, FSH, and TSH are composed of two noncovalently linked subunits, alpha and beta. The beta-subunit confers hormone specificity, while the alpha-subunit is homologous within a species. To help in determining the antigenic structure of the common alpha-subunit, six monoclonal antibodies (mAbs) to the free or heterodimeric alpha-subunit of human (h) gonadotropic hormones have been prepared and, along with two previously isolated mAbs, have been characterized for binding specificity to alpha- and beta-subunits and the human glycoprotein hormones, CG, LH, FSH, and TSH. Each mAb was derived from hybidomas of FO myeloma cells fused with spleen cells from mice immunized with free alpha-subunit, hCG or hFSH. mAbs A101, A102, and E512 were specific for the alpha-subunit but showed the highest affinity for the intact hormone; K2.18, K94.6, E501, E502, and E511 were specific for free alpha. All of the antibodies inhibited binding of 125I-hCG to luteal membrane receptor, and 125I-labeled mAbs did not recognize hCG/receptor complex. Characterization by two-site binding assays using alpha, hCG, or hFSH as antigen revealed that all the mAbs bind to unique sites on alpha which may be overlapping, and which are modified in the intact hormone. The antigenic sites for mAbs E502, E511, and K2.18 are at least partially linear because they bind to reduced, carboxymethylated alpha.

Sequential serum measurements of thyrotropin binding inhibitor immunoglobulin G in transient familial neonatal hypothyroidism.

Infants with transient neonatal hypothyroidism, in whom TSH binding inhibitor immunoglobulin G (IgG) (TBII) were sequentially measured, are described. Their mother had been taking thyroid replacement for hypothyroidism due to nongoitrous autoimmune thyroiditis. IgGs inhibiting TSH binding were detected in maternal sera by radioreceptor assay. These IgGs also inhibited the adenylate cyclase response to TSH in human thyroid membranes. Three infants had frank hypothyroidism immediately after birth, and TBII were detected in two of them. In the two surviving infants, hypothyroidism was transient and improved when TBII disappeared from their sera. The profile of TBII in one patient corresponded to the IgG disappearance curve. These findings suggest that the transient neonatal hypothyroidism reported was caused by transplacental transfer of TBII.

Recent progress in the solid-phase synthesis of glycopeptide.

The recent understanding of the biological role of glycoproteins has brought about a demand for the highly homogeneous glycopeptides as the functional model for glycoproteins. Thus, much efforts have been made to establish easy and efficient method for glycopeptide synthesis. In this paper, we briefly review the recent advances in the synthesis of O- and N-linked glycopeptide based on the solid-phase method. In O-glycopeptide section, the preparation of glycosylated amino acid units with mucin type and other O-linked carbohydrate chains and their use for solid-phase synthesis are summarized. Other approaches, such as the glycosylation of resin bound peptide are also overviewed. In N-glycopeptide section, the synthesis using glycosylated amino acid units as well as other methods are described.

Functional and possible physical association of scavenger receptor with cytoplasmic tyrosine kinase Lyn in monocytic THP-1-derived macrophages.

Acetyl LDL (modified low-density lipoprotein), which is thought to be taken up through scavenger receptor A (SR-A), rapidly induced the appearance of phosphotyrosine proteins in monocytic THP-1-derived macrophages in vitro. The two alternative forms of Lyn (p53 and p56) were found to be tyrosine-phosphorylated within 30 s after the stimulation with acetyl LDL. The catalytic activity of Lyn measured by an in vitro kinase assay had also increased in acetyl LDL-stimulated THP-1-derived macrophages. Furthermore, Lyn could be co-immunoprecipitated with SR-A from the cell lysate. These observations suggest a functional and possible physical association of SR-A with Lyn in THP-1-derived macrophages, and also imply a possible involvement of Lyn in SR-A signal transduction.

Predictive value of serum interleukin-6 level in influenza virus-associated encephalopathy.

OBJECTIVE: In Japan, >200 children with influenza virus-associated encephalopathy were reported in 1999 and the mortality rate was high. The levels of tumor necrosis factor-alpha (TNFalpha) and interleukin-6 (IL-6) in both CSF and serum were significantly increased in severe cases. The authors found a correlation between elevated serum cytokine levels and mortality and neurologic morbidity. METHODS: TNFalpha, IL-6, soluble tumor necrosis factor receptor 1 (sTNF-R1), interferon-gamma (IFNgamma), and IL-2 were measured by the ELISA method in sera from six children with encephalopathy before and during therapy, and in six age-matched controls with influenza type A virus infection. RESULTS: The increases in the serum TNFalpha, IL-6, and sTNF-R1 levels were statistically significant at the onset of symptoms before therapy, but the IL-6 level was most useful for diagnosis. The serum IL-6 levels were >6,000 pg/mL in children with brain stem dysfunction, about 150 pg/mL in children without brain stem dysfunction, and <80 pg/mL in controls. The time course of the serum IL-6 level also reflected the clinical condition. Once the serum IL-6 level was increased to >15,000 pg/mL, none of the children survived. The lower the maximal serum IL-6 level, the milder the CNS sequelae. CONCLUSION: The serum IL-6 level may be the most useful indicator for the diagnosis and the clinical severity of influenza virus-associated encephalopathy.

Low-dose ACTH therapy for West syndrome: initial effects and long-term outcome.

BACKGROUND: Most Japanese pediatric neurologists attempt other treatments before using adrenocorticotropic hormone (ACTH) therapy for West syndrome (WS), and even then, they use only a low-dose synthetic ACTH to avoid serious adverse effects. In this multi-institutional study, the authors analyzed the initial effects, adverse effects, and long-term outcome in patients treated with low-dose synthetic ACTH in Japan. METHODS: The medical records of 138 patients with WS, who were treated with low-dose synthetic ACTH therapy for the first time at the authors' institutions between 1989 and 1998, were analyzed. RESULTS: At the end of ACTH therapy, excellent effect on seizures was noted in 106 of 138 (76%) patients, good effect in 23 (17%), and poor effect in 9 (7%). Initial effects on EEG were excellent in 53 of 138 (38%) patients, good in 76 (55%), and poor in 9 (7%). As for seizure prognosis at the time of follow-up, 51 of 99 (52%) patients were seizure-free, whereas 48 (48%) patients had seizures. Mental outcome was normal in 6 of 98 (6%) patients, mild mental retardation in 16 (16%), moderate mental retardation in 26 (27%), and severe mental retardation in 50 (51%). The initial effects of ACTH on seizures and long-term outcome were not dose dependent (daily dosage 0.005 to 0.032 mg/kg, 0.2 to 1.28 IU/kg; total dosage 0.1 to 0.87 mg/kg, 4 to 34.8 IU/kg). The severity of adverse effects correlated with total dosage of ACTH, and the severity of brain volume loss due to ACTH correlated well with the daily dosage and total dosage of ACTH. CONCLUSION: Low-dose synthetic ACTH therapy is as effective for the treatment of WS as the higher doses used in previous studies. The dosage of synthetic ACTH used in the treatment of WS can be decreased as much as possible to avoid serious adverse effects.

Rhabdoid papillary meningioma.

We have studied an uncommon case of rhabdoid papillary meningioma in a 15-year-old boy with a dura-based mass arising in the left posterior fossa. The patient exhibited prominent extracranial extension during the past 6 years, consisting of a mixture of both perivascular pseudopapillary growth and rhabdoid cytologic features of neoplastic meningothelial cells. The meningothelial features were evidenced by the focal whorl formation of tumor cells, coexpression of epithelial membrane antigen and vimentin, and ultrastructural findings of interdigitated cytoplasmic process and intercellular junction. However, the regional and histologic resemblances to ependymoma were further complicated by unexpected focal expression of glial fibrillary acidic protein, neurofilament, and alpha-smooth muscle actin of the tumor cells. The rhabdoid morphology was characterized by sheets of tumor cells with eccentric nuclei and abundant eosinophilic cytoplasm with often recognizable intracytoplasmic hyaline inclusions. These inclusions revealed ultrastructural paranuclear whorls of intermediate filaments, ruling out the other forms of intracytoplasmic eosinophilic inclusions resembling rhabdoid morphology. Diagnosis of an unusual rhabdoid papillary meningioma with aggressive behavior is resoluble by immunohistochemical and ultrastructural analyses.

Pseudosarcomatous myofibroblastic tumor of the urinary bladder in children: a study of 11 cases with review of the literature. An Intergroup Rhabdomyosarcoma Study.

Pseudosarcomatous myofibroblastic tumor (PMT) is the result of reactive proliferation of myofibroblasts. In children, PMT of the urinary bladder can be mistaken for embryonal rhabdomyosarcoma clinically, radiologically, and by light microscopy. We are reporting the clinical, histological, and immunohistological features of 11 patients with childhood PMT of urinary bladder that were diagnosed initially as a sarcoma, usually rhabdomyosarcoma. The morphologic spectrum of PMT is broad, with mixtures of myxoid, leiomyomatous, and sclerosing matrix patterns, the myxoid type being the most common. The proliferating cells consist of three forms of myofibroblastic cells: long spindle cells (type I), intermediate spindle cells (type II), and ganglion-like cells (type III), together with various types of inflammatory cells. The immunohistologic profile of the proliferating cells was characterized by positive reactions to vimentin, muscle-specific actin, alpha-smooth-muscle actin, polyclonal desmin, and keratin. Ultrastructural studies showed myofibroblastic differentiation of the tumor cells. No patients have had metastases or local recurrence. Histologic, immunohistochemical, and clinical data from 71 cases of PMT, including the 11 cases in this report, confirm the benign behavior of these lesions. The etiology of these lesions is unclear, including the absence of surgical or other trauma in all of the children.