INVESTIGATION OF A PRACTICAL PATIENT DOSE INDEX FOR ASSESSMENT OF PATIENT ORGAN DOSE FROM CONE-BEAM COMPUTED TOMOGRAPHY IN RADIATION THERAPY USING A MONTE CARLO SIMULATION.

The purpose of this study was to investigate a practical patient dose index for assessing the patient organ dose from a cone-beam computed tomography (CBCT) scan by comparing eight dose indices, i.e. CTDI100, CTDIIEC, CTDI∞, midpoint doses f(0)PMMA for a cylindrical polymethyl methacrylate (PMMA) phantom, f(0)Ap for an anthropomorphic phantom and f(0)Pat for a prostate cancer patient, as well as the conventional size specific dose estimations (SSDEconv) and modified SSDE (SSDEmod), with organ dose for the prostate (ODprost) obtained via Monte Carlo (MC) simulation. The ODprost was the reference dose used to find the practical dose index at the center of the pelvic region of a prostate cancer patient. The smallest error rate with respect to the ODprost of 19.3 mGy (reference) among eight dose indices was 5% for f(0)Pat. The practical patient dose index was the f(0)Pat, which showed the smallest error with respect to the reference dose.

Myxoid angioblastomatosis of bones. A case report of a rare, multifocal entity with light, ultramicroscopic, and immunopathologic correlation.

An example of multicentric, skeletal, myxoid angioblastomas in a Japanese woman is reported. The disease was symptomatic at age 12 years and was characterized by slowly progressive, multiple, lytic bone defects. In addition the patient had juvenile hypertension, and, at age 20 years, had focal brain infarction. The primitive vascular nature of the process was supported by the following observations: occasional erythrocytes within cytoplasmic lumina and capillary-like cellular tubes; Weibel-Palade bodies, numerous pinocytotic vesicles, prominent microvilli, elaborate intercellular contacts, desmosomes, and numerous arrays of fine intracytoplasmic filaments by electron microscopy; and, in addition, Factor VIII positivity. The clinical findings in this case are more consistent with a multicentric, rather than a metastatic process. The name myxoid angioblastomatosis of bones is appropriate.

Primary osteosarcoma of toe phalanx: first documented case. Review of osteosarcoma of short tubular bones.

A case of a sclerosing variant of osteosarcoma of a toe phalanx is reported in a 28-year-old man. This represents the first reported case of osteosarcoma of any kind at this site. This is based on a review of 4,214 cases of conventional osteosarcoma. The reason for the extraordinary rarity in toe or hand phalanges is unknown although osteosarcoma is the second most common primary tumor of bone. Since the neoplasm had minimal signs of cytologic anaplasia, it was originally mistaken for and treated as an osteoid osteoma. The lesion recurred and extended into soft tissues. Reevaluation revealed the tumor to be an osteosarcoma, sclerosing variant with "normalization" of nuclei. The lesions that this tumor should be distinguished from are osteoid osteoma and osteoblastoma.

Malignant glomus tumor: a case report and review of the literature.

This report concerns a malignant glomus tumor, a rare soft tissue tumor that was examined immunohistochemically and ultrastructurally. It occurred in a 44-year-old male patient who had suffered from dull pain and stiffness in the right thigh for 10 months. Radiographic examination revealed a well-defined osteolytic lesion in the diaphysis of the right femur. Hypervascularity of the tumor was observed angiographically. Computed tomographic and magnetic resonance examinations showed an intramuscular mass invading the marrow space of the femur. Wide resection was performed after open biopsy. Histologically, round to polygonal tumor cells revealed a uniform appearance of round to ovoid nuclei with single large nucleoli and slightly eosinophilic cytoplasm, forming solid sheets of cells interrupted by vessels of varying size. A few mitotic figures and vascular invasion were observed. Immunohistochemically, vimentin and alpha-smooth muscle actin were stained intensely, and muscle actin was positive for tumor cells of the perivascular area. Tumor cells were negative for desmin, factor VIII-related antigen, S-100 protein, neurofilament, cytokeratin, and epithelial membrane antigen. Ultrastructurally, tumor cells were characterized by many cytoplasmic processes, pinocytotic vesicles, plasmalemmal dense plaques, and scattered microfilaments in the cytoplasm. Few cell junctions and focal basement membrane-like structures were observed. No recurrence or metastasis was noted 57 months after operation. This case was considered to be a malignant glomus tumor, that is, a glomangiosarcoma arising de novo.

Developmental regulation of myotonic dystrophy protein kinase in human muscle cells in vitro.

From our previous studies, myotonic dystrophy protein kinase: gene product of myotonic dystrophy is localized at the terminal cisternae of sarcoplasmic reticulum of human adult muscle. Now we have studied the developmental expression of myotonic dystrophy protein kinase in aneurally cultured human muscles and contracting cross-striated muscles innervated with fetal rat spinal cord using a semi-quantitative reverse transcription-polymerase chain reaction method for myotonic dystrophy protein kinase messenger RNA expression, Western blot analysis, immunohistochemical examinations by laser scanning confocal microscopy and immunoelectron microscopy. About 65,000 mol. wt myotonic dystrophy protein kinase was detected in aneurally cultured muscles. Myotonic dystrophy protein kinase messenger RNA was expressed in both aneurally and innervated cultured muscles, but in early innervated cultured muscles the message was transiently lower than in aneurally cultured muscles and innervated cultured muscles in long-term co-culture. In aneurally cultured muscles, immature aneurally cultured muscles show a diffuse and irregular distribution of myotonic dystrophy protein kinase in the deeper cytoplasm near the nuclei. Ultrastructurally the immuno-products against myotonic dystrophy protein kinase were observed as dense deposits in parts of the membranes near the mitochondria. In innervated cultured muscles, immunofluorescent microscopy showed myotonic dystrophy protein kinase to be localized regularly in the I bands and A-I junctions. Ultrastructurally myotonic dystrophy protein kinase was localized in branched duct-like membranes in the early stage of innervated cultured muscles and then in small sacs at the I bands and A-I junctions of the sarcolemma in the mature stage. Our present studies strongly suggest that innervation plays an important role in the localization of myotonic dystrophy protein kinase in human skeletal muscle during development. We conclude that the expression of myotonic dystrophy protein kinase during development is under neuronal influence.

Developmental studies of dystrophin and other cytoskeletal proteins in cultured muscle cells.

We studied the developmental changes of localization of dystrophin and other cytoskeletal proteins, especially actin, spectrin and dystrophin related protein (DRP) using immunocytochemistry and quick-freezing and deep-etching (QF-DE) method. In developmental studies of mouse and human muscle cultures, some myoblasts had positive-reactions to spectrin, DRP, and F-actin, but not dystrophin. In aneurally cultured myotubes, dystrophin, DRP, and spectrin were localized diffusely in the cytoplasm and later in discontinuous patterns on the plasma membrane, when myotubes became mature. Spectrin and DRP had more positive reactions in immature myotubes, compared with those of dystrophin. In some areas of myotubes, dystrophin/spectrin and spectrin/actin were localized reciprocally. In innervated cultured human muscle cells, dystrophin and DRP were localized in neuro-muscular junctions, which were co-localized with clusters of acetylcholine receptors. By using the QF-DE method, dystrophin was localized just underneath the plasma membrane, and closely linked to actin-like filaments (8-10 nm in diameter), most of which were decorated with myosin subfragment 1. In actin-poor regions, spectrin was detected as well-organized filamentous structures in highly interconnected networks with various diameters. DRP was distributed irregularly with granular appearance inside the cytoplasm and also under the plasma membrane in immature mouse myotubes. Our present studies show that dystrophin, spectrin, and DRP are localized differently at the developmental stages of myotubes. These results suggest that dystrophin, spectrin, and DRP are organized independently in developing myotubes and these cytoskeletal proteins might play different functions in the preservation of plasma membrane stability in developing myotubes.

A case of therapy-related acute myeloblastic leukemia with t(16;21)(q24;q22) after chemotherapy with DNA-topoisomerase II inhibitors, etoposide and mitoxantrone, and the alkylating agent, cyclophosphamide.

A 59-year-old female suffering from malignant lymphoma developed therapy-related acute myeloblastic leukemia (t-AML) after chemotherapy consisting of treatment with DNA-topoisomerase II inhibitors, etoposide and mitoxantrone, and an alkylating agent, cyclophosphamide. The cumulative dose of etoposide administration was 5500 mg; 1500 mg given intravenously and 4000 mg orally. One year later, she suddenly developed AML of FAB M2. Cytogenetic analysis of bone marrow cells revealed deletion of 7q and a rare translocation, t(16;21)(q24;q22). Southern blot analysis of bone marrow cells did not detect rearrangement of the AML1 gene, however, fluorescence in situ hybridization (FISH) analysis of bone marrow cells at interphase and metaphase revealed a translocational splitting between chromosome 21 involving AML1 gene and chromosome 16. These results suggest that the breakpoint is not located in the breakpoint cluster region for t(8;21). The patient was treated with chemotherapy and entered complete remission.

Morphological and cytogenetic changes in therapy-related leukemia developed in a t(8;21)-acute myeloid leukemia (M2) patient: sequential cytogenetic and molecular analyses.

A patient with acute myeloid leukemia (AML)-M2 with t(8;21)(q22;q22) achieved complete remission with remission-induction chemotherapy followed by consolidation and intensification chemotherapies. T(8;21)(q22;q22) disappeared, but chimeric AML1/MTG8 was continuously detected in bone marrow cells. Following the development of therapy-related leukemia after 1 year, evolution of therapy-related AML-M4 with t(11;17)(q23;q25) and the rearrangement of the MLL gene were observed, while AML/MTG8 disappeared. After reinduction and following intermittent chemotherapies, a subsequent alternative transformation to AML-M2 occurred after detection of t(3;21)(q21;q22), with a break in the AML1 gene shown by interphase fluorescence in situ hybridization analysis. This leukemia transformed to AML-M4 after t(9;22)(q34;q11), with a minor BCR/ABL rearrangement, and then finally to AML-M2. This therapy-related leukemia was resistant to chemotherapy. These findings indicate that alterations in cytogenetic and molecular events caused by chemotherapeutic agents contribute to the sequential evolution of new leukemic clones with different morphology.

Granulocyte colony-stimulating factor (G-CSF) dependent hematopoiesis with monosomy 7 in a patient with severe aplastic anemia after ATG/CsA/G-CSF combined therapy.

We report a case of secondary myelodysplastic syndrome (MDS) with monosomy 7, which evolved from severe aplastic anemia (SAA) after long-term use of granulocyte colony-stimulating factor (G-CSF). A 36 year old female was admitted for detailed examination and treatment of pancytopenia. SAA was diagnosed based on hypoplastic bone marrow and a normal chromosome study. She was treated with anti-thymocyte globulin (ATG), ciclosporin A (CsA) and G-CSF, which resulted in gradual improvement of not only the myeloid but also the erythroid-megakaryocyte series. However, bone marrow dysplasia with monosomy 7 was observed after 7 months of a combination therapy of immunosuppressant and G-CSF, which prompted the discontinuation of G-CSF administration. Thereafter, bone marrow hypoplasia gradually progressed, resulting in a second aplastic crisis. During this process, the proportion of marrow cells showing monosomy 7 decreased, and the proportion with normal karyotype increased. Re-administration of G-CSF induced a trilineage, though dysplastic, hematological response; but the monosomy 7 positive population increased again. These observations indicated the presence of G-CSF dependent hematopoiesis associated with monosomy 7 in this patient. Although many G-CSF related MDS/AML cases with this leukemia-specific abnormal karyotype have been reported with emphasis on the harmful effects of G-CSF, G-CSF was useful even after the appearance of monosomy 7 as a means of avoiding life-threatening infection in this patient.

Developmental study of the expression of dystrophin in cultured human muscle aneurally and innervated with fetal rat spinal cord.

So far there have been no developmental studies including the influences of innervation and contractile activity on the expression of dystrophin in cultured human muscle. We performed immunocytochemical studies of the localization of dystrophin on aneurally cultured non-contracting (AMs) and innervated continuously contracting cross-striated human muscle fibers (ICMs) with fetal rat spinal cord from normal and Duchenne muscular dystrophy (DMD) biopsied muscles. In normal AMs, myoblasts and some immature AMs showed negative staining of dystrophin, but many AMs had a patchy (discontinuous) distribution of dystrophin in the subplasmalemmal region and with some granularity near the sarcolemma and in the deeper cytoplasm. In normal ICMs, dystrophin was localized continuously at the inner aspect of the sarcolemmal membrane and some periodic dense patterns were detected in some areas. Both AMs and ICMs from DMD had negative staining of dystrophin. To investigate the muscle contractile activity on the distribution of dystrophin, we paralyzed ICMs with tetrodotoxin (TTX) for two weeks from the first appearance of muscle contractions. In paralyzed innervated muscles (PIMs), dystrophin remained in a patchy (discontinuous) pattern at the inner aspect of the plasmalemma similar to that in AMs. It is strongly suggested that muscle contractile activity plays an important role in the continuous and even distribution of dystrophin at the sarcolemma during development.

Human myasthenia gravis thymic myoid cells: de novo immunohistochemical and intracellular electrophysiological studies.

Thymic myoid cells from myasthenia gravis (MG) patients and controls were successfully grown in explant cultures: we have compared them with skeletal muscle cells cultured from biopsies in morphological, immunohistochemical and electrophysiological studies. Some mononucleate cells in thymus cultures were myoglobin- or desmin-positive, but they were much rarer than the otherwise similar fusing myoblasts in muscle cultures. Frequencies of cultured myoglobin-positive cells showed no difference between MG and control and male or female, but were lower in samples of malignant thymoma, in younger cases and in those with less severe MG. Electrophysiologically the resting membrane potentials of cultured thymic multinucleate cells were significantly less than those of cultured skeletal muscle cells, and action potentials by electrical stimulation were rarely observed. In thymus cultures from only one case with malignant thymoma, desmin-positive myotubes had spontaneous irregular contractions followed by electrical firings. It is concluded that there are myoid cells in MG and control thymuses which have the potential to become skeletal muscle fibers morphologically and electrophysiologically, although their frequency and proliferation in culture are quite low.

Developmental studies of the expression of myosin heavy chain isoforms in cultured human muscle aneurally and innervated with fetal rat spinal cord.

To study the influence of innervation of human muscle fiber type differentiation, we performed immunohistochemical studies using three monoclonal antibodies (McAbs) to myosin heavy chain (MHC) on cultured human muscles at different developmental stages. McAbs QM 355 (McAb-1), E 35-3 (McAb-2) and SM 1-11-2 (McAb-3) bound to fiber types I, IIA, IIB and IIC, types IIA, IIB and IIC, and type I, respectively. At the mononucleated cell stage the majority was immunonegative to the three McAbs; however, a few myoblasts were immunopositive to the McAb-1. They were also weakly stained with McAb-2 but not with McAb-3. In aneurally cultured myotubes (AMs), all myotubes were stained with the McAb-1 and 92.1% of AMs were positive to the McAb-2, whereas only a few (0.9%) AMs were immunopositive to the McAb-3. In contracting muscle fibers in an innervated area (CMis), which were co-cultured with fetal rat spinal cord explants, the percentage of the McAb-3-positive CMis was significantly increased (8.3%; P < 0.01) compared with that of AMs (0.9%). The double staining with the McAbs-2 and -3 clearly showed that slow MHC-positive muscle fibers without fast MHC only appeared in CMis. This is the first report of the neuronal influence on the expression of human adult slow MHC isoform derived from adult human satellite cells in vitro.

Decreased expression of myotonic dystrophy protein kinase and disorganization of sarcoplasmic reticulum in skeletal muscle of myotonic dystrophy.

Pathological expression of myotonic'dystrophy protein kinase (DMPK) in skeletal muscle of myotonic dystrophy (DM) was studied by Western blot analysis, immunohistochemistry, and immunoelectron microscopy of DMPK. Western blot analysis showed that DMPK protein in DM skeletal muscles dramatically decreased. DMPK-positive muscle fibers showed typical DM pathological changes such as type I atrophy, central nuclei, nuclear chains, and sarcoplasmic masses. In degenerated DMPK-positive muscle fibers, cross-striated bands disappeared, and irregular granular DMPK-positive materials appeared in sarcoplasm. By immunoelectron microscopy, DMPK was localized in the terminal cisternae of the sarcoplasmic reticulum (SR) in DM muscle. Swollen DMPK-positive SRs were detected between well preserved myofibrils in the early stage of DM muscle degeneration, and degenerated intramembranous structures with DMPK and an accumulation of mitochondria were observed between disorganized myofibrils in degenerated DM muscle. We concluded that SR is the primary site of the degeneration of DM skeletal muscle and that the decreased DMPK might cause dysregulation of intracellular calcium metabolism, which is followed by DM muscle degeneration.

Plasma cadmium-metallothionein, a biological exposure index for cadmium-induced renal dysfunction, based on the mechanism of its action.

Thirteen rabbits were given subcutaneous cadmium (0.3 mg Cd/kg) daily. The plasma cadmium-metallothionein (CdMT) and the Cd-induced hepatic and renal functions were determined at 0, 5, 8, 11, 12, 13 and 14 weeks. Hepatic dysfunction, an elevated plasma CdMT and renal dysfunction were detected mostly between 12 and 14 weeks. The hepatic dysfunction parameters were closely related with the plasma CdMT, which was then found to correlate with the renal dysfunction parameters. All the above findings suggest the following mechanism for the Cd-induced renal dysfunction: hepatic CdMT is released into the plasma upon the Cd-induced hepatic dysfunction, and then excess plasma CdMT, whose concentration is proportional to the CdMT in the renal proximal tubular lumen, induces renal dysfunction. The critical concentration of plasma CdMT to induce renal dysfunction was estimated as 80 microg Cd/l. The plasma CdMT is proposed therefore as a biological exposure index for the Cd-induced renal dysfunction, based on the mechanism of its action.

Mechanism of hepatorenal syndrome in rats of Long-Evans Cinnamon strain, an animal model of fulminant Wilson's disease.

Rats of Long-Evans Cinnamon (LEC) strain were used as a hepatorenal syndrome model of fulminant Wilson's disease. Copper levels in the kidneys increased markedly from 16 to 126 microg Cu/g from 12 to 16 weeks, and remained at the same level at 16 and 19 weeks when the rats suffered from severe renal dysfunction and also at 20 weeks in some other normal rats. The above findings imply that the renal dysfunction may have been induced independently of the copper level in the kidneys. The present study suggested the following mechanism: immediately after copper-induced hepatic dysfunction, plasma copper-metallothionein (CuMT), which was released from the liver, became elevated. The elevation was closely related to the increases in alkaline phosphatase, glucose and amino acids, all in the urine. The above findings suggest that plasma CuMT, which was released from the liver into the blood upon copper-induced hepatic dysfunction, was subsequently filtered at the glomeruli due to its smaller molecular weight, and then caused dysfunction of the brush border membrane of the renal proximal tubules probably after splitting into radical copper and amino acids in acidic vesicles close to the membrane. The critical concentration of plasma CuMT required to induce renal dysfunction was estimated as 1 microg Cu/l.

TMC-171A,B,C and TMC-154, novel polyketide antibiotics produced by Gliocladium sp. TC 1304 and TC 1282.

Four new antibiotics, TMC-171A (2), B (3), C (4) and TMC-154 (5) have been isolated from the fermentation of fungal strains Gliocladium sp. TC 1304 and TC 1282, respectively. Spectroscopic and degradation studies have shown that TMC-171s and TMC-154 were new members of the TMC-151 class of antibiotics, unique polyketides modified with a D-mannose and a D-mannitol or a D-arabitol. These compounds showed moderate cytotoxicity to various tumor cell lines.

Two cases of myelodysplastic syndrome with extramedullary polyclonal plasma cell proliferation and autoantibody production: possible role of soluble Fas antigen for production of excessive self-reactive B cells.

Two cases of myelodysplastic syndrome (MDS) with extramedullary polyclonal plasma cell proliferation and autoantibody production are reported. These cases, which showed leukemic change of refractory anemia with excess of blast (RAEB), developed lymph node swelling and muscle abscess; both were infiltrated mainly with plasma cells, without preceding infection. The proliferation of plasma cells was polyclonal and was proven by negative rearrangement of immunoglobulin heavy chain gene or polyclonal staining of immunoglobulin light chains. These patients showed polyclonal gammopathy and autoantibody production such as positive antinuclear factor and direct antiglobulin test. As was observed in one of the present cases, and as we reported previously, the elevated level of soluble Fas antigen in MDS patients, and its inhibition of apoptotic signaling may be responsible for the excessive accumulation of self-reactive B cells, resulting in these clinical manifestations.

[Hematoma of the pineal region: a case report].

A 44-year-old man came to our clinic, complaining of slowly progressive disturbance of visual acuity and of ocular movement. This patient suffered from headache, narrowing of visual field and polyuria about 20 years ago, and received surgical and radiation therapy under the diagnosis of pituitary adenoma. Clinical symptoms and signs of this patient, except for bitemporal hemianopsia, almost completely disappeared after these treatment. The detailed information about the histology and radiation dose are not available at the present time. CT scan in our clinic revealed a round low-density area at the suprasellar region and a high density area at the left quadrigeminal cistern. Pineal calcification was compressed to the right about 2-3 mm from midline. This high density mass were not enhanced with contrast medium. Vertebral angiography showed a slight lateral displacement of the left medial posterior choroidal artery. Specimen of tissue removed 20 years ago was reexamined but definitive diagnosis could not be established. Presumptive diagnosis of an ectopic pinealoma in the suprasellar region treated successfully 20 years ago, and its recurrence in the pineal region was made. On May 24, the patient underwent a posterior fossa craniectomy and the pineal region was explored via the infratentorial supracerebellar approach. On sectioning the precentral cerebellar vein, yellowish mass was seen in the quadrigeminal cistern. Aspiration of this mass yielded dark red liquid hematoma. Incising into the capsule, a dark brownish mass of about 4g was removed en bloc.(ABSTRACT TRUNCATED AT 250 WORDS)

[Syphilitic orchitis: report of a case].

Syphilitic orchitis ir recently a rare disease in Japan. A 44-year-old man visited our hospital with the complaint of swelling of the right scrotum. He first noticed it about a half year ago, but the swelling mitigated without any therapy. The right testis was about the size of a hen's egg, elastic hard, and slightly rugged when he first visited our hospital. Treponema pallidum hemagglutination assay (TPHA) and rapid plasma reagin (RPR) were positive. We performed high orchiectomy because we could not deny the possibility of testicular tumor. Pathologically, granulomatous inflammation with lympho-plasmacytic infiltration and endoarteritis obliterans of the small arteries were seen in the specimen. It was diagnosed as granulomatous inflammation possibly caused by syphilitic orchitis. Syphilitic orchitis is usually quite difficult to distinguish from other types of granulomatous diseases of the testes, for example tuberculous orchitis. Various types of stains and careful examination of the specimen were thought to be necessary to distinguish these diseases.

[Bilateral multilocular cystic renal cell carcinoma].

A case of bilateral renal cell carcinoma with multilocular cysts is described. A 42-year-old female was admitted to our hospital for the purpose of further examination or right renal cystic mass discovered incidentally by ultrasonography. After she was examined by CT-scan and angiography, right nephrectomy was performed under the diagnosis of right renal cancer. Histological diagnosis was multilocular cystic renal cell carcinoma. One year later a small cystic legion was found in the left kidney. Under the diagnosis of left renal cancer, left partial nephrectomy was performed. Histological diagnosis was multilocular cystic renal cell carcinoma same as the right kidney. Multilocular renal cyst is classified into several classes by its style of development. This case of bilateral renal cell carcinoma which grew to be multilocular cysts is the first case in Japan as far as we can search.