An autopsy case of intravascular malignant lymphoma presenting with intracranial B-cell type malignant lymphoma.

This report concerns a 79-year-old man with intravascular malignant lymphoma who was admitted to our hospital for slight right side hemiparesis. Radiological examinations showed a mass in the left parietal lobe, and a brain biopsy revealed a B-cell type malignant lymphoma. The tumor could not be detected on magnetic resonance images following focal radiotherapy, but the patient died of acute progressive pneumonia about 3 months after the onset of symptoms. An autopsy was performed. Microscopic examinations disclosed proliferation of neoplastic cells in the small and medium-sized blood vessels of the adrenal glands, liver, spleen, pancreas, kidneys and epididymis. A diagnosis of intravascular malignant lymphoma was established on the bases of these autopsy findings.

[Chondrosarcoma of the skull base associated with fatal intratumoral hemorrhage : report of an autopsy case and review of the literature].

We report a case of intracranial chondrosarcoma of the skull base with fatal intra- and peritumoral hemorrhage. A 75-year-old woman complained of right blepharoptosis and diplopia in 1989. An initial diagnosis of Tolosa-Hunt syndrome was made, and the patient was treated with steroid hormone therapy at a local hospital. Because the symptoms had not been relieved, she was admitted to our hospital. Computed tomography (CT) scan and magnetic resonance (MR) images demonstrated a large mass extending from the right side of the clivus to the parasellar region and petrous apex. The mass was partially calcified and had destroyed the base of the middle cranial fossa. The lesion had homogeneous enhancement with contrast medium. Preoperative diagnosis was chordoma or chondroma. A biopsy of the tumor was made. The pathological diagnosis of biopsy specimen was chondroid chordoma. The patient was followed up but no palliative treatment such as radiotherapy was given. On June 25, 1991, she suffered from cerebral infarction. On June 29, 1993, she died of sudden respiratory failure. Autopsy was performed. It revealed intra- and peritumoral hematoma compressing the medulla oblongata, pons and midbrain. Histologically immature chondroid cells proliferated in a myxoid-rich extracellular matrix. The tumor cells were composed of hyperchromatic nuclei and eosinophilic cytoplasm, but there was no evidence of notochordal differentiation. Compared with biopsy findings, the tumor showed high cellular density. Immunohistochemically, the tumor cells reacted positively for S - 100 protein, vimentin and cytokeratin, but negatively for epithelial membrane antigen (EMA) and carcinoembryonic antigen (CEA). In view of these histopathological findings, the diagnosis of low-grade myxoid chondrosarcoma was established. Intratumoral hemorrhage often occurs in malignant brain tumors such as glioblastoma and metastatic brain tumor, but chondroid tumors rarely develop a fatal type of intratumoral hemorrhage. Only 8 cases have been reported in detail to date. We discuss the immunohistochemical features and spontaneous intratumoral hemorrhage of chondrosarcoma.

Distribution of DNA cleavages induced by bleomycin and neocarzinostatin in a defined sequence of rat glioma cells.

We have demonstrated the usefulness of a highly reiterated sequence of rat DNA as a probe sequence for evaluating the effect of bleomycin (BLM) and neocarzinostatin (NCS) at the level of individual nucleotides. The 370 base pairs (bp) DNA fragment, purified from rat glioma C6 cells after Hind III digestion, was labeled with 32P at either the 3'- or the 5'-ends and then divided into 167 bp and 203 bp by Hae III. These end-labeled DNA fragments were reacted in vitro with BLM or NCS, and electrophoresed on the denaturating 8% polyacrylamide gels according to Maxam and Gilbert's sequencing protocol. BLM created DNA strand breaks at the guanine-cytosine and guanine-thymine (5'----3') sequences, and NCS cleaved DNA at the position of thymines and adenines. The highly reiterated sequence of rat brain tumor DNA therefore provides adequate knowledge of DNA damages induced by BLM and NCS.

Primary pituitary carcinoma with spinal cord metastasis--case report.

The authors report a rare case of non-functioning pituitary carcinoma with spinal cord metastasis. A 37-year-old female presented with a 2-month history of right retro-orbital ache and vomiting. She had a pituitary adenoma removed 3 years prior to admission. Neuroradiologically, a mass lesion was demonstrated in the right middle cranial fossa. The tumor was removed through craniotomy and was histologically diagnosed as pituitary carcinoma. One week after the operation, tetraplegia developed and CT scans demonstrated a spinal canal lesion. Although the tumor was removed through C3-C7 laminectomies, she gradually deteriorated and died. At autopsy, a tumor was disclosed in the right temporal lobe and basal ganglia. Moreover, the tumor invaded into the middle cranial fossa and the parasellar region.

Linkage between O6-methylguanine-DNA methyltransferase (O6-MT) activity and cellular resistance to antitumour nitrosoureas in cultured rat brain tumour cell strains.

We have examined O6-methylguanine-DNA methyltransferase (O6-MT) activity of rat brain tumour cell strains with reference to cellular resistance to antitumour nitrosoureas, 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride (nimustine, ACNU) and methyl-6-[3-(2-chloroethyl)-3-nitrosoureido]-6-deoxy-alpha-D-glucopyrano side (ramustine, MCNU). The values of O6-MT activity were 52 and 160 fmol/mg protein extract in 9L and C6 rat brain tumour cells, respectively; while HeLa S3 cells, as a methyl excision repair positive (Mer+) cell strain, revealed a rather high value of 488 fmol/mg. 9L cells indicative of a low O6-MT activity showed 13 microM for ACNU and 18 microM for MCNU at a 10% survival dose (SD10), determined by a clonogenic cell assay as an index of cellular resistance. In contrast to this, C6 cells revealed a SD10 value of 67 microM and 36 microM for ACNU and MCNU, respectively, indicating higher resistance than 9L cells. HeLa S3 cells showed the highest SD10 value as follows: 84 microM for ACNU and 73 microM for MCNU. The relationship between the O6-MT activity and the cellular resistance was almost linear, with relatively resistant cell lines exhibiting the higher levels of the O6-MT activity. This correlation between the O6-MT activity and the cellular resistance to nitrosoureas as ACNU and MCNU was not observed among other antitumour drugs, which included bleomycin (BLM), neocarzinostatin (NCS), cis-diamminedichloroplatinum (II) (CDDP), and etoposide (VP-16) in clinical use for brain tumour chemotherapy. This indicates that O6-MT activity can be an indicator of cellular resistance to antitumour nitrosoureas in the chemotherapy of brain tumours.

[Chemotherapeutic strategy in rat brain tumor cells resistant to ACNU using an in vitro colony formation assay].

Nitrosourea compounds have been widely used in the chemotherapy of malignant brain tumors, because of their blood-brain barrier permeability. However, drug resistance to nitrosoureas has been recently a major concern. Using an in vitro colony formation assay, intrinsic and acquired resistances to an anticancer nitrosourea, 1-(4-amino-2-methyl-5-pyrimidinyl) methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride (ACNU), were analyzed in rat 9L and C6 glioma cells. 9L and C6 cells were treated with varying doses of ACNU for 2 hours. Ten days after, the cells were fixed and stained with crystal violet. Colonies consisting more than 50 cells were counted. The survival fraction following treatment is the ratios of colony efficiency of treated cells to the colony efficiency of untreated control cells. The dose-response curve for ACNU indicated the existence of a shoulder (Dq, quasithreshold dose) at doses and an exponential cell-killing at higher doses with D0(37% survival dose). Based on dose-response curves corresponding to multitarget single-hit model, 9L cells showed 7.4 microM, 2.9 microM, and 14 microM at Dq, D0, and SD10 (10% survival dose) values, respectively, whereas C6 cells showed respective values of 6.4 microM, 30 microM, and 75 microM. 9L cells had significantly less intrinsic resistance to ACNU than C6 cells at the p less than 0.005 level by a covariance analysis of the curves. As with changes of drug susceptibility after ACNU treatment, both parent cells were treated every other day (1, 5, and 10 repeated times) with various doses up to approximately 1% survival dose of the parent cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Studies on a new herbicidal antibiotic, homoalanosine.

Homoalanosine having a herbicidal activity was isolated from the culture filtrate of a soil isolate SC-1688 which was classified as Streptomyces galilaeus. The chemical structure of homoalanosine was determined to be L-2-amino-4-nitrosohydroxyaminobutyric acid by analyses of spectral and biological data. The antibiotic has high herbicidal activity at low concentrations against especially common cocklebur and ladysthumb among the tested weeds and crops. Foliar application of this antibiotic inhibited the growth of roots and buds. This result indicated that homoalanosine had a systemic herbicidal activity.

Studies on new phosphate ester antifungal antibiotics phoslactomycins. I. Taxonomy, fermentation, purification and biological activities.

New antibiotics phoslactomycins A, B, C, D, E and F, which contain alpha, beta-unsaturated delta-lactone, phosphate ester, conjugated diene and cyclohexane ring moieties, were isolated from the culture broth of a soil isolate actinomycete. Morphological, cultural and physiological studies revealed that the isolate is a strain of Streptomyces nigrescens. Phoslactomycins were obtained by butanol extraction, gel filtration and reverse phase chromatography. The antibiotics show strong activity against various fungi, particularly phytopathogenic fungi (Botrytis cinerea and Alternaria kikuchiana).

Studies on new phosphate ester antifungal antibiotics phoslactomycins. II. Structure elucidation of phoslactomycins A to F.

Phoslactomycins A to F are new antifungal antibiotics produced by Streptomyces nigrescens SC-273. On the basis of physico-chemical properties and NMR studies, their structures have been determined as shown in Fig. 6. They are characterized by possessing alpha, beta-unsaturated delta-lactone, phosphate ester, conjugated diene and cyclohexane ring moieties. The structural difference between them is ascribed to a substituent bound to the cyclohexane ring.

Microspectrofluorometric evaluation of single- and double-stranded DNA in short-term cultured human glioma cells.

Seven cerebral gliomas in short-term culture were studied by microspectrofluorometry and acridine orange staining to assess their nuclear content of single- and double-stranded DNA. Benign gliomas showed a diploid DNA pattern, whereas malignant gliomas revealed a higher frequency of DNA aneuploidy and hyperploidy. The content of single-stranded DNA remained relatively low in benign gliomas; however, that in malignant gliomas varied widely. After ACNU treatment, the double-stranded DNA histograms showed S-phase-specific accumulation in all cases but 1 with increasing concentrations of ACNU. The single-stranded DNA content decreased considerably in 2 cases, which responded well to chemotherapy and showed clinical amelioration.

[Circumvention of ACNU-resistance in rat glioma cells by pretreatment with O6-methylguanine].

The chemotherapy of malignant brain tumors has been, only partially successful yet. Recently major concern is drug resistance, one of possible mechanisms of such drug resistance stems from inducible repair enzyme, especially in case of chloroethylnitrosoureas as ACNU or BCNU. We examined the changes of acquired resistance to ACNU in rat glioma cells by pretreatment with O6-methylguanine, which is a substrate for O6-methylguanine methyltransferase. ACNU-resistant (9L/AC) cells had established after 10 times treatments of ACNU. 9L/AC cells were pretreated with 2 mM O6-methylguanine for 2 hours, and subsequently challenged with increasing doses of ACNU for 2 hours. In vitro colony formation assay the survival fraction of 9L and 9L/AC cells ranged from 0.39 to 0.63 by 2-hour reaction of 1-3 mM O6-methylguanine. Based on the dose-response curve for ACNU in 9L/AC cells, by O6-methylguanine pretreatment (2 mM), ACNU-resistance decreased markedly to one-third, one-fifth, and one-two hundredth at 12, 24, 36 microM ACNU, respectively. In contrast, the survival of 9L cells against ACNU was similar under O6-methylguanine pretreatment or nontreatment condition. Therefore, ACNU-resistance is considerably related to DNA repair enzyme induction, and the substrates may potentiate the cell-killing effect of ACNU in the resistant glioma cells.

DNA lability induced by nimustine and ramustine in rat glioma cells.

The DNA labile sites induced by two nitrosoureas, nimustine (ACNU) and ramustine (MCNU) synthesised in Japan, have been examined in highly reiterated DNA sequences of rat glioma cells. Reiterated fragments of 167 and 203 base pairs (bp), obtained after Hind III and Hae III restriction endonuclease digestion of rat glioma cells DNA, were used as target DNA sequences to determine the labile sites. In vitro reaction with ACNU and MCNU resulted in scission products corresponding to the locations of guanine. Subsequent piperidine hydrolysis produced more frequent breaks of the phosphodiester bonds at guanine positions, thus forming alkali-labile sites.

In vitro damage of isolated DNA from two brain tumor cell lines induced by a water-soluble antitumor nitrosourea.

We report the DNA sites damaged by the antitumor drug, nimustine hydrochloride (ACNU), in highly reiterated DNA sequences of rat glioma cells. A reiterated fragment of 370 base pairs (bp), obtained after Hind III restriction endonuclease digestion of rat glioma C6 or 9L cells DNA, was divided into 167 and 203 bp by subsequent Hae III enzyme reaction. The reaction of end-labelled 167 and 203 bp fragments with ACNU resulted in scission breaks corresponding to the locations of guanine. Moreover, ACNU and subsequent piperidine hydrolysis produced more frequent breaks of the phosphodiester bonds at the guanine positions, thus forming alkali-labile sites. These results indicate that the preferred site of DNA strand scission induced by ACNU is at guanine positions.

[Analysis of DNA damage induced by nitrosourea derivatives in rat brain tumor cells using a sequencing procedure].

DNA damages caused by various anticancer nitrosourea compounds such as ACNU and MCNU were studied. Reiterated fragments of 167 and 203 base pairs (bp) were obtained after Hind III and Hae III restriction endonuclease digestion of 9L rat brain tumor DNA. The end-labeled reiterated fragments were reacted with ACNU and MCNU, which resulted in the scission breaks corresponding to the locations of guanine on an extended Maxam-Gilbert sequencing gel. Subsequent piperidine hydrolysis yielded scission products more frequently. These results indicate that nitrosoureas such as ACNU and MCNU generate DNA scission breaks and/or alkali-labile sites preferentially at the position of guanine moieties in rat brain tumor DNA.

Detection of DNA sites damaged by 1-(4-amino-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride (ACNU) using a DNA sequencing procedure.

A DNA sequencing technique was applied to the highly reiterated DNA from HeLa S3 cells in order to detect DNA damage induced by the antitumor drug, 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride (ACNU). A DNA reiterated fragment of 92 base pairs (bp) was isolated by gel electrophoresis after EcoRI and EcoRI restriction endonuclease digestion. In the defined sequence of the 92 bp fragment, ACNU caused damage and modifications primarily at guanine moieties, leading to alkali-labile sites as determined by subsequent piperidine reaction on an extended Maxam-Gilbert sequencing gel. These results indicate that guanine moieties in double-stranded DNA are preferentially vulnerable to ACNU over other base moieties.

[A case of trigeminal neurinoma with marked extracranial extension].

A case of trigeminal neurinoma with marked extracranial extension is reported with a review of the literature. A 60-year-old female noticed numbness over the left side of the face during the proceeding 15 years. Two years prior to admission, she began to complain of itching and lancinating pain at the left lateral aspect of the nose. Neurologic examination on admission revealed diminished corneal reflex on the left side and hypesthesia in the distribution of the left trigeminal nerve. There was no weakness or atrophy of the ipsilateral masticatory muscles. The remaining cranial nerves and cerebellar functions were normal. Craniograms showed destruction of the left petrous apex, enlargement of the left superior orbital fissure and an extensive bone defect in the floor of the left middle cranial fossa. CT disclosed a huge heterogeneously enhancing mass lesion in the left middle cranial fossa, which extended posteriorly into the left cerebellopontine angle and inferiorly into the pterygoid and infratemporal fossae. Cerebral angiograms revealed medial displacement of the left internal cerebral artery in the ganglionic, cavernous and supraclinoid portions, and elevation of the left middle cerebral artery in the sphenoidal portion. Although the left meningohypophyseal trunk was dilated, no tumor stain was observed. A transantral biopsy specimen provided the diagnosis of neurinoma with Antoni type A tissue. The patient was followed up at the outpatient clinic as radical operations were not agreed upon. Eight cases of trigeminal neurinoma with extracranial extension are reviewed including the presented case. There were two males and six females, and the age varied from 16 to 65 years.(ABSTRACT TRUNCATED AT 250 WORDS)