Search

Donor cell-derived leukemia (DCL) is a rare complication of SCT. Here, we present a case of DCL following cord blood transplantation (CBT) and review the clinical features of previously reported DCL. To our knowledge, this is the first report comparing clinical characteristics of DCL from the standpoint of the transplant source, with umbilical cord blood and BM. AML and myelodysplastic syndrome (MDS) were recognized more frequently in DCL after CBT, whereas the incidence of AML and ALL was similar after BMT. The median duration between the occurrence of DCL following CBT and BMT was 14.5 and 36 months, respectively. DCL occurred in a significantly shorter period after CBT than after BMT. Abnormal karyotypes involving chromosome 7 were observed in 52.4% of CBT recipients and 17.3% of BMT recipients; this was a statistically significant difference. Particularly, the frequency of monosomy 7 was significantly higher in DCL after CBT than after BMT. The types of abnormal karyotypes in DCL following BMT were similar to those characteristically observed in adult de novo AML and MDS. DCL patients generally have a poor prognosis in both groups. SCT is the best treatment for curing DCL. DCL appears to have different clinical features according to the transplant source.

Aims : Most lymphomas arising in the nasal cavity are thought to be of natural killer (NK) cell origin. However, some reports indicate that T- and B-cell lymphomas may also primarily arise in the nasal cavity. We therefore studied lymphomas arising in the nasal cavity both histologically and immunohistochemically. Methods and results : Of the 32 cases investigated, 20 cases were also available as fresh frozen specimens. We diagnosed 31 cases as extranodal NK/T-cell lymphoma and one as plasmacytoma. The neoplastic cells were immunoreactive for CD3 (polyclonal) 31/31, LMP-1 12/31, CD20 (L26) 0/31, granzyme B 30/31, TIA-1 30/30, CD56 (123C3) 29/31, CD4 0/31 and CD8 3/31. In situ hybridization for Epstein–Barr virus-encoded small RNA-1 (EBER-1) was detected in 31/31. In frozen tissue sections, neoplastic cells mostly showed CD3 (Leu4)–, CD4 (Leu3a)–, CD5 (Leu1)–, CD8 (Leu2)–, CD16 (Leu11)–, CD56 (Leu19)+, βF1–, TCRδ1–, perforin+, CD94+ phenotypes. These immunohistochemical findings indicate their NK cell origin. In three cases, neoplastic cells were positive for CD8. In one of these cases, neoplastic cells were positive for CD8β and Vα24, suggesting their NKT-cell origin. Conclusions : Our present study indicates that primary lymphomas arising in the nasal cavity are mostly of NK cell derivation. Our present study also suggests that a small number of cases are derived from NKT-cells.

The first urine in the morning (total 15 samples) and whole day urine (total 4 days, 17 samples) were collected from a young healthy woman during the pregnancy and lactation period, to examine the possible interactions of urine components (methanol extracts) with P-glycoprotein (P-gp) and multidrug resistance-associated proteins (MRPs). The interaction was evaluated by measuring the intracellular accumulation of rhodamine123, a P-gp substrate, in LLC-GA5-COL150 cells, or calcein, an MRP substrate, in Caco-2 cells in the absence and presence of urine components. Four first urine samples out of 12 collected before childbirth and one sample out of three collected after childbirth suppressed P-gp function significantly. The effect of pregnancy and lactation on P-gp inhibitory potencies of urine components was not observed. The whole day urine samples showed a clear circadian rhythm, in which three first urine samples in the morning out of four showed greater P-gp inhibitory potencies than other daytime samples. Interaction of urine components with MRPs was not detected. In conclusion, the concentration of endogenous P-gp inhibitor(s) was higher in the first urine in the morning, showing a clear circadian rhythm. Normal pregnancy and lactation appeared not to significantly affect the P-gp inhibitory potencies of urine components.

We encountered a case of tracheal stenosis post tracheostomy, so-called cuff stenosis. A 43-year-old man with ventricular septal defect (VSD) was treated by oral endotracheal intubation because of heart-failure and pneumonia, and tracheostomy was performed. He was placed on artificial ventilation for almost 3 months. Four months after discharge, he complained of dyspnea and was treated by oral endotracheal intubation again. At that time bronchofiberscopy demonstrated severe circumferential stenosis of the trachea 4 cm from the tracheostomy spot and that was compatible with the cuff site. Although the stenotic portion was dilated by an endotracheal tube, 47-days after dilation, the portion was restenosed to almost 7 mm in diameter. Therefore, surgical treatment was necessary and tracheoplasty was performed by end-to-end suture after 2 cm (4 ring) resection of trachea. Tracheoplasty is the most reliable method of treating cuff stenosis after tracheostomy.

BACKGROUND AND PURPOSE: We hypothesized that diffusion tensor fiber tractography would be affected by intracranial arteriovenous malformation (AVM). The purpose of the present study was to evaluate the influence of intracranial AVM on corticospinal tract and optic radiation tractography. MATERIALS AND METHODS: The subject group comprised 34 patients with untreated intracranial AVM. Hemorrhage was present in 13 patients and absent in 21 patients. Perinidal fractional anisotropy (FA) and number of voxels along the reconstructed corticospinal and optic radiation tracts were measured, and left-to-right asymmetry indices (AIs) for those values were quantified. Patients were assigned to 1 of 3 groups: tracts distant from nidus, tracts close to nidus without neurologic symptoms, and tracts close to nidus associated with neurologic symptoms. One-way analysis of variance was used to compare differences in AI between groups. Hemorrhagic and nonhemorrhagic groups were assessed separately. RESULTS: In patients without hemorrhage, AI of optic radiation volume (P < .0001), AI of perinidal FA along corticospinal tract (P = .006), and optic radiation (P = .01) differed significantly between groups. In patients associated with hemorrhage, AI of corticospinal tract volume (P = .01), AI of perinidal FA along corticospinal tract (P = .04), and optic radiation (P = .004) differed significantly between groups. CONCLUSIONS: Corticospinal tract and optic radiation tractography were visualized in patients with AVM. In patients with both hemorrhagic and nonhemorrhagic AVM, the 2 fiber tracts close to the nidus were less visualized in the affected hemisphere than those distant from the nidus. Tracts were less visualized in patients with neurologic symptoms than in asymptomatic patients.

Eight patients with large vestibular aqueduct (LVA) syndrome and acute sensorineural hearing loss that had not responded to intravenous treatment were treated with hyperbaric oxygen(HBO2) therapy. This was performed daily, with 15 treatments per course. Pure tone and speech audiometry were performed on all patients. The mean hearing recovery following HBO2 therapy (20.8 +/- 12.1 dB) was significantly higher than after intravenous treatment (2.3 +/- 7.2 dB) (P0.01), although treatment duration was not different between the two therapies. Of the eight patients, five showed complete or partial recovery after one course of HBO2 therapy, and their hearing levels have not since changed. The other three patients showed heating recovery during therapy, but treatment had to be repeated for two or more courses because of progressive or fluctuating hearing loss.We consider HBO2 therapy should be used to treat acute hearing deterioration associated with LVA syndrome if patients do not recover their hearing ability following conventional treatment

We evaluated the usefulness of 99mTc-methoxy-isobutyl-isonitrile (MIBI) dual phase scintigraphy for detecting hyperfunctioning parathyroid adenoma. We retrospectively reviewed 18 hyperparathyroid patients who received MIBI prior to neck exploration and compared the radiological findings of MIBI with ultrasonography (US) and magnetic resonance imaging (MRI). Fifteen patients were studied with MRI, and 17 patients were examined with US. All patients were found to have a solitary parathyroid adenoma histopathologically. MIBI correctly revealed the location of 17 adenomas among 18 confirmed tumors. In our series, there was one false-positive case that was found to have thyroid adenoma. The diagnostic sensitivity of MIBI MRI and US was 94.4%, 80% and 52.5%, respectively. The positive predictive value (PPV) was 94.4% for MIBI, 81.8% for MRI and 92.3% for US. We conclude that MIBI is useful and accurate for the preoperative localization of adenoma in primary hyperparathyroidism.

Our previous report (T. Hayashibara et al., Leukemia, 13: 1634-1635, 1999) revealed a possible link between high plasma vascular endothelial growth factor (VEGF) concentration and leukemic cell invasion in adult T-cell leukemia (ATL). However, the biological mechanism of this link has not been elucidated. The purpose of this study was to address that mechanism. Our present observations showed that VEGF mRNA was expressed in ATL cell lines. The corresponding protein was secreted into the extracellular environment, which suggested that the major source of plasma VEGF is ATL cells themselves. More interestingly, all of the cell lines examined were found to express the mRNA and protein for fms-like tyrosine kinase-1 (Flt-1), which is one of the receptors for VEGF. Cytofluorometric analysis demonstrated the VEGF binding potency of these cells. In clinical specimens, expression of VEGF and Flt-1 mRNAs was detected in all (100%) of 11 and 8 (73%) of 11 ATL patients, respectively. Cytofluorometric analysis revealed that VEGF effectively bound only to Flt-1-expressing cells. These findings are highly suggestive of an autocrine pathway involving VEGF operating in ATL. The proliferation of ATL cell lines was not affected by treatment with an anti-VEGF antibody or exogenous VEGF, which indicated that VEGF has no mitogenic effect on ATL cells. In contrast, we made the interesting finding that treatment with exogenous VEGF enhanced the chemotactic activities of some ATL cell lines, which may play a key role in ATL cell invasion. Collectively, these data lead us to propose a possible autocrine mechanism involving VEGF operating by way of Flt-1, in which ATL cells up-regulate their own chemotaxis to facilitate their invasion into various organs.

There have so far been no studies that directly compared clinical features between patients with early- and late-onset anorexia nervosa (AN).We identified 64 patients with DSM-III-R AN. We defined individuals as an early-onset group, who had an age of onset before 14 years (N = 31), and the remaining as a late-onset group (N = 33). The clinical symptoms, body weight and weight index, were compared between the two groups. Subjects were dichotomized into those with extremely low weight and those remaining. We compared the proportion of the patients with extremely low weight between the two groups.The rates of 'self-induced vomiting' and 'purging' were significantly lower in a group of patients with early-onset AN than in those with late-onset AN. There were significantly fewer subjects with extremely low weight in early-onset than in late-onset AN group.We found clear differences in clinical features between early- and late-onset AN groups.

We analyzed the clinicopathological features of 5 Japanese patients with CD56+ primary cutaneous lymphomas (3 men and 2 women aged 25 to 73 years). Except for 1 patient in whom bone marrow involvement was simultaneously observed, all patients presented with cutaneous lesions. Based on their Epstein-Barr virus (EBV) status, we categorized these patients into 2 groups, namely EBV-encoded small RNA-1 (EBER-1) (3 patients) and EBER-1- (2 patients). Generalized lymphadenopathy and bone marrow involvement were observed only in EBER-1 patients. Morphologically, angiocentric proliferation was more prominent in EBER-1+ patients and was accompanied by panniculitis-like changes. The lymphomas in EBER-1- patients featured monomorphic proliferation of lymphoblastic cells with no cytoplasmic granules. Phenotypically, CD3-, cytoplasmic CD3 epsilon+, and CD56+ were common findings in both types. The EBER-1- type showed an additional distinguishing feature, CD7+, CD4+, CD8-, HLA-DR+, and terminal deoxynucleotidyl transferase-positive (TdT+) phenotype. The lymphoma was primarily resistant in the EBER-1+ type, and the patients died within 6 months of admission. In contrast, the lymphoma in the EBER-1- patients was originally chemosensitive. Collectively, we consider there to be at least 2 types of CD56+ primary cutaneous lymphomas, corresponding to nasal-type natural killer (NK)/T-cell lymphomas (EBER-1+) and blastic NK-cell lymphomas (EBER-1-).

Continuous systemic infusion of low-dose cisplatin (CDDP) (10 mg/body/day) and 5-fluorouracil (5-FU) (500 mg/body/day) was performed for advanced hepatocellular carcinoma (HCC) after hepatectomy with diffuse lung metastases and multiple intrahepatic metastases. This infusion chemotherapy, cisplatin was continued for five days, and discontinued for two days, whereas 5-fluorouracil was administered every day and repeated four weeks as one course basally. Remnant metastases had almost disappeared after systemic chemotherapy for 10 weeks. In our experience, the response rate in 13 patients who underwent reduction surgery for multiple HCC was 84.6%. Continuous infusion of low-dose CDDP/5-FU may be effective in patients having absolute non-curative resection.

A 39-year-old woman was admitted to our hospital because of advanced hepatocellular carcinoma. She had good liver function with clinical Stage I. Abdominal ultrasonographic study and CT scan revealed a huge tumor of 12 cm in diameter in the left lobe of the liver, with tumor thrombi in the portal and hepatic veins. A chest CT scan demonstrated multiple bilateral lung metastases from 5 to 10 mm in size. An extended left hemihepatectomy with extirpation of the portal and hepatic venous tumor thrombi was performed. On postoperative day 7, low-dose cisplatin (10 mg/day-5 days/week) and 5-fluorouracil (250 mg/day-continuous for 7 days/week) were administered intravenously. Four weeks after chemotherapy, CT scan revealed no recurrence in the liver and no change in the lung metastases. The patient is now being treated on an outpatient basis with no change in the metastatic tumors.

Anaplastic large cell lymphoma (ALCL) is a distinct entity of non-Hodgkin lymphoma, characterized by a proliferation of pleomorphic large lymphoid cells that express CD30. Recent studies have found that a subset of ALCL aberrantly expresses a chimeric anaplastic lymphoma kinase (ALK) protein as a result of t(2;5)(p23;q35) or variant translocations. ALK-positive ALCLs feature good prognosis, but some of them lead to poor outcomes. Since CD56 is expressed in some ALCLs, its clinical significance was examined in a series of T/null cell type ALCLs. Of 143 patients, 83 (58%) showed ALK-positive staining, and of 140 patients, 25 (18%) expressed CD56. The ALK-positive subgroup was characterized by a younger age of onset (P.0001), lower serum lactate dehydrogenase level (P =.01), better performance status (P =.03), less frequent extranodal involvement (P =.01), lower international prognostic index (IPI) categories (P =.002), and superior survival (P =.0009) in comparison with the ALK-negative group, suggesting that ALK is a specific marker defining a distinct subtype. CD56(+) cases showed a significantly poor prognosis overall (P =.002) as well as in both ALK-positive and ALK-negative subgroups (P =.02 and P =.04, respectively). Multivariate analysis confirmed that CD56 is independent of other prognostic factors, including IPI. Although CD56(+) cases showed a higher incidence of bone involvement, no other differences in clinicopathologic parameters were found between the CD56(+) and CD56(-) groups. These findings suggest that CD56 is not a marker to identify a distinct subtype of ALCL, but a strong clinical prognostic factor. Effective therapeutic approaches should be explored for high-risk ALCL patients, who can be identified by means of a prognostic model, including CD56.

Aggressive natural killer (NK) cell leukaemia will be categorized as a distinct entity in the new WHO classification of malignant lymphomas. However, its non-leukaemic features remain unclear. We therefore investigated the morphological and immunophenotypic features of this lymphoma.Four cases with aggressive NK cell lymphoma were morphologically and immunohistochemically studied. All cases followed an aggressive course with death occurring within about 3 months of initial presentation. In these cases, the neoplastic cells disseminated throughout systemic lymph nodes and invaded various tissues and organs. The lymphoma cells were large cells showing nuclear irregularity and a pattern of sinusoidal invasion in lymph nodes. Apoptosis and coagulation necrosis were both frequently observed. Haemophagocytosis was observed in all cases. Neoplastic cells in paraffin-embedded tissue specimens from these patients had CD3(CD3epsilon)+ CD56(123C3)+ granzyme+ TIA-1+ EBERT+ CD43(MT1)- CD45RO(UCHL-1)- CD57(Leu7)- CD20(L26)- phenotypes. In the two cases where tissue was available for immunohistochemical study in frozen sections, neoplastic cells showed CD56(Leu19)+ perforin+ Fas ligand(FasL)+ CD2(Leu5b)- CD3(Leu4)- CD4(Leu3)- CD5(Leu1)- CD7(Leu9)- CD8(Leu2)- betaF1- TCRdelta1- phenotypes. CD16(Leu11b) was positive in one case.: Natural killer cell lymphomas appear to represent a non-leukaemic counterpart of aggressive natural killer cell leukaemia, a relationship similar to that in adult T-cell leukaemia/lymphoma. Awareness and diagnosis of this aggressive lymphoma is important because of its fulminant course.

Lactacystin (LC) is a specific inhibitor of the proteasome, and has recently been shown to induce apoptosis in certain cell lines. In the present study, we established Fas-resistant adult T-cell leukemia (ATL) cell subclones RSO4 and RST1 from their parental Fas-sensitive cell lines SO4 and ST1, and examined whether LC can overcome Fas resistance. LC completely inhibited proteasome function as determined by a peptidyl-MCA substrate (LLVY-MCA and LLE-MCA), and induced apoptosis in these cell lines irrespective of Fas sensitivity at low concentrations (approximately 10 microM). LC induced the activation of caspase 3 (CPP32/Yama) and caspase 6 proteases in an identical manner to Fas-mediated apoptosis. Moreover, LC induced the activation of caspase 8 (FLICE) protease, which is the initiator of the Fas-mediated apoptotic cascade. Synthesized proteasome inhibitory peptide MG-115 (ZLLnV-CHO) also induced apoptosis in these cell lines. These results indicated that proteasome inhibitors overcome Fas-resistance by bypassing the proximal part of the Fas signal. Inhibition of the proteasome function may be a new strategy for the treatment of ATL.

Human T-cell leukemia virus type-I (HTLV-I) is the etiologic agent of adult T-cell leukemia (ATL). This study examined the status of the oncogenic transcription factor AP-1 in leukemic cells freshly isolated from patients with ATL. Leukemic cells from peripheral blood of all patients with ATL exhibited constitutive AP-1 DNA binding activity, whereas mononuclear cells from normal individuals did not. In agreement with previous studies, HTLV-I transforming protein, Tax, was found to stimulate the DNA binding activity of AP-1 in a T-cell line. However, HTLV-I genes, including Tax, were not significantly expressed in leukemic cells freshly obtained from patients with ATL. Moreover, all T-cell lines derived from leukemic cells of patients with ATL also displayed constitutive AP-1 DNA binding activity, but expressed little Tax protein. Thus, leukemic cells of patients with ATL appear to have Tax-independent mechanisms that induce AP-1 activity, both in vivo and in vitro. In antibody supershift experiments, AP-1 in fresh leukemic cells and ATL-derived cell lines were found to contain JunD. Consistently, all primary ATL cells and ATL-derived cell lines expressed high levels of JunD messenger RNA. Our results suggest that AP-1 is activated in leukemic cells of patients with ATL through a Tax-independent mechanism and this may play a role in the deregulated phenotypes of ATL leukemic cells. (Blood. 2000;95:3915-3921)

Recent analyses have suggested that Hodgkin's or Reed-Sternberg (HRS) cells in most cases of classic Hodgkin's disease are derived from germinal centre B-cells. However, there is controversy over which B-cell antigens are expressed in HRS cells.We studied 51 cases of classic Hodgkin's disease to immunohistochemically characterize HRS cells for pan-B-cell markers and specific markers for plasma cells. HRS cells expressed CD20 (L26) in 18 cases (35%), CD19 (B4) in nine (18%) and CD79a (mb-1) in 13 (25%). Furthermore, HRS cells were positive for CD138 (B-B4) in 24 cases (45%) and for PCA-1 in 24 (45%). In 41 (80%) cases, HRS cells expressed more than one B-cell marker. We then subclassified cases into those positive for plasma cell markers (n = 27) (group 1) and those negative for them (n = 24) (group 2). The average age in group 1 (40 years) was younger than in group 2 (54 years) (P0.05). The percentage of nodular sclerosis (NS) subtype in group 1 (52%) was 1.5 times greater than in group 2 (33%) (P0.05). With regard to Epstein-Barr virus encoded small RNA (EBER) in-situ hybridization, 14 cases (64%) were positive in group 2, but only seven cases (31%) were positive in group 1 (P0.025).In most cases of classic Hodgkin's disease, HRS cells expressed later stage of B-cell development. We consider that two different clinicopathological groups may correlate with the two different expressions of B-cell markers.

Two adult Japanese patients with severe solar urticaria are reported. In both patients, an action spectrum existed in the visible light range, and an augmentation spectrum was demonstrated in the visible light range longer than the action spectrum. The augmentation phenomenon has rarely been documented, and in the previous reports, it was induced by preirradiation with the augmentation spectrum. In our cases, however, only postirradiation with the augmentation spectrum enhanced urticarial reactions.

We performed a neuropathological examination of the central nervous system from seven autopsied patients with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS). Five of the seven cases were confirmed to have the mitochondrial DNA (mtDNA) 3243 point mutation. In addition to the changes reported previously, diffuse atrophy of the cerebral and cerebellar cortices, diffuse gliosis of cerebral and cerebellar white matter, and cactus formation of Purkinje cells were observed. Electron microscopy revealed accumulation of mitochondria in the cactus formations. These lesions are common in MELAS with the mtDNA 3243 point mutation, but cannot be explained solely by mitochondrial angiopathy, and suggest that intrinsic mitochondrial malfunction contributes to neuronal damage in MELAS pathology. Moreover, the pathological changes observed in the cerebellum suggest that cerebellar function should be evaluated more carefully at the clinical level.

Tuberous sclerosis is associated commonly with renal angiomyolipoma. On the other hand, the relation between tuberous sclerosis and renal cell carcinoma is not widely recognized. We report a case of renal cell carcinoma of the right kidney associated with tuberous sclerosis.

We studied the morphologic and immunohistochemical features of 10 peripheral T-cell lymphomas of a cytotoxic phenotype (CD3+/CD4-/CD8+), encountered among 98 peripheral T-cell lymphomas (PTCLs). Nine tumors were positive for both cytotoxic molecules, namely perforin (Pf) and granzyme B (GrB), and strong positivity was seen in the majority of the malignant cells. We also studied the expression of these molecules in 92 other cases of T-cell and natural killer (NK) cell neoplasms; 18 anaplastic large cell lymphomas (ALCLs); 63 CD4+ PTCLs; 10 CD56+ nasal lymphomas; and 1 NK-cell leukemia. Most of the CD4+ PTCLs (62 of 63) were negative for GrB, but all of the nasal lymphomas and the NK cell leukemia were positive for both Pf and GrB. Variable expression was seen among the 18 ALCLs. Within the 10 CD8+ PTCLs, 4 involved the skin, 3 of which were diagnosed as primary cutaneous lymphomas. Five patients died within 1 year of diagnosis. According to the Revised European-American Classification of Lymphoid Neoplasms, seven cases were categorized as "PTCL, unspecified," and three as "angioimmunoblastic T-cell lymphoma," "adult T-cell lymphoma/leukemia," or "small cell lymphoma," respectively. Three cases had characteristic morphologic features consisting of large lymphomatous cells with massive necrosis and nuclear fragmentation. Epstein-Barr virus mRNA was detected by in situ hybridization in three cases. Although the degree of apoptosis varied, apoptotic cells were detected in all cases by terminal deoxynucleotidyl transferase-mediated deoxyuridine 5-triphosphate-biotin nick end labeling. We conclude that CD8+ PTCLs are relatively rare, often involve extranodal sites, have an aggressive clinical course, and are often associated with Epstein-Barr virus. Compared with ALCLs, which have recently been considered as neoplasms of cytotoxic T-cells, we think that CD8+ PTCLs are more lineage-specific neoplasms of mature, cytotoxic, T lymphocytes.

We examined 20 cases (21 specimens) of ocular adnexal lymphoid proliferations, using the histological, immunohistochemical and molecular genetic methods. The latter two protocols were performed to detect the light chains restriction of immunoglobulin with peroxidase-antiperoxidase (PAP) methods, and the clonality of immunoglobulin heavy chain gene with the hemi-nested polymerase chain reaction (PCR) method, respectively. Although in 8 cases it could not be morphologically determined whether they were neoplastic or not, clonality was revealed in 1 case with immunohistochemistry and in 4 cases with PCR. Two cases showed discordant results between immunohistochemistry and PCR probably due to somatic mutation of the framework region of the immunoglobulin heavy chain gene. Therefore, we, concluded that examination with these methods contribute to a better understanding of the nature of the ocular adnexal lymphoid proliferations. Furthermore, the immunoglobulin gene PCR method is very useful in practical examination, as it can be used with formalin-fixed paraffin-embedded specimens.

By computerized static posturography, the subclinical effects of past and concurrent lead absorption on the vestibulo-cerebellum (lower vermis), anterior cerebellar lobe and spinocerebellar afferent pathway were examined in 49 male chemical factory workers exposed to lead stearate (lead workers). Their concurrent blood lead (BPb) concentrations ranged from 7 to 36 (mean 18.0) microgram/100 g. In the past, their maximum BPb ranged from 11 to 113 (mean 47.7) micrograms/100 g; mean BPb was 7-52 (mean 23.5) micrograms/100 g; and cumulative BPb, defined as mean BPb x years of exposure, was 15-1268 (mean 390.6) micrograms.year/100 g. Control subjects were 23 healthy male workers who had never been occupationally exposed to lead. The postural sway of high (2-4 Hz) and low (1 Hz or less) frequencies with eyes open for lead workers was significantly greater than that for controls in the medio-lateral (right-left) and anterior-posterior directions. Similarly, the sway of high and low frequencies with eyes closed was significantly larger in lead workers than in controls in the medio-lateral direction. Results of stepwise multiple regression analysis indicated that the sway with frequencies of 0.5-2 Hz with eyes open was related to concurrent BPb in the anterior-posterior direction. With eyes closed the sway of high frequency was significantly related to mean BPb in the past in the medio-lateral direction. The pattern of the changes suggests that the vestibulo-cerebellum, anterior cerebellar lobe and spinocerebellar pathway are asymptomatically affected by lead. It appears that the change in the vestibulo-cerebellum reflects concurrent lead absorption, while on the other hand, that in the anterior cerebellar lobe reflects past lead absorption.

Eight patients with nasal lymphoma in whom fresh-frozen tissues were available were studied to elucidate the nature of the lymphoma cells. Two cases were diagnosed as diffuse, large cell lymphoma, and the remaining six cases as diffuse, mixed cell types. Immunohistochemical studies revealed that all of the cases were positive for perforin, which is a specific marker for cytotoxic T or natural killer (NK) cells. As all of the cases were CD8 negative, the perforin-positive finding further confirmed the concept that nasal lymphoma is a distinct neoplastic entity derived from NK or NK-related cells. Light microscopic immunohistochemical studies revealed that these nasal lymphoma cases could be classified into Leu19(CD56)+Leu4(CD3)+ (two cases) and Leu19(CD56)+Leu4(CD3)- (six cases) types according to the phenotypes of the proliferating cells. However, simultaneous staining for perforin and Leu4 (CD3) using immunoelectron microscopy on the Leu19+Leu4+ cases showed that the perforin-positive cells were different from the Leu4-positive cells. This finding suggests that the Leu4-positive cells are not neoplastic NK cells but reactive T cells. Six cases were positive for EBER-1 by in situ hybridization analysis. This finding reconfirms the previous studies that Epstein-Barr virus plays a significant role in the pathogenesis of nasal lymphoma.

Bilateral striatal necrosis in acute encephalopathy has been reported in a small number of adults with methanol or cyanide intoxication, hypoxic encephalopathy or haemolytic-uraemic syndrome. Acute encephalopathy with bilateral striatal necrosis has been reported in infants and children. However, the pathogenesis of the necrosis remains unclear. This is the first report of serial imaging from the very early to chronic stage in two acute encephalopathic adults with bilateral striatal necrosis. A clinicoradiological study is presented for clarification of the pathological process and pathogenesis. Striatal lesions were not detected in the very early stages, but only thereafter. Serial studies suggested that the lesions were caused by delayed neuronal death. These patients had severe lactic acidosis, near the limit for survival. There have been few reports of adults with acute encephalopathy and bilateral striatal necrosis in whom arterial pH was described; all these exhibited marked acidosis. The common pathophysiological condition among these encephalopathies with bilateral striatal necrosis could be lactic acidosis elicited by impairment of ATP generation through the Krebs cycle. The striatum might represent one of the target areas of Krebs-cycle blockade.

Human T-cell leukemia virus type I (HTLV-I) is the etiological agent for adult T-cell leukemia and tropical spastic paraparesis/HTLV-I-associated myelopathy. Recently, the transcription factor AP-2 has been demonstrated to be capable of activating gene expression from HTLV-I long terminal repeat. To determine whether changes occur in the levels of AP-2-binding activity in HTLV-I-infected cell lines, we compared the levels of AP-2 binding of nuclear extracts obtained from HTLV-I-infected T-cell lines with those of nuclear extracts obtained from uninfected T-cell lines. High levels of AP-2-binding activity were observed in HTLV-I-infected cell lines (MT-2, HUT-102, and SLB-1) using the mobility shift assay. In contrast, in the uninfected cell lines (Jurkat, HUT-78, and MLA 144), AP-2-binding activity was obviously low compared with that in the HTLV-I-infected cell lines. HTLV-I transactivator protein tax activates expression of both viral and cellular genes. We have demonstrated further that introduction of the tax gene into Jurkat cells stimulated AP-2-binding activity. These results indicate that HTLV-I-infected T cells exhibit constitutive AP-2-binding activity, and that tax may increase the DNA binding activity of AP-2.

Systemic scleroderma is a disorder of unknown etiology with skin sclerosis. Its major histological features are swollen and homogenized collagen bundles.We describe 2 patients with systemic sclerosis who have multiple umbilicated nodules indistinguishable from calcinosis cutis.Histological examinations including Von Kossa staining revealed features of perforating granuloma annulare, but not of calcinosis cutis.The association may not be fortuitous but both diseases may be etiologically related.

Anaplastic large cell lymphoma (ALCL) is a subtype of non-Hodgkin's lymphoma characterized by the CD30+ large neoplastic cells and sometimes carries a t(2;5)(p23;q35). Recently, we found a novel hyperphosphorylated 80-kD protein tyrosine kinase, p80, in ALCLs with t(2;5). Subsequent cDNA cloning showed p80 to be a fusion protein of two genes, the novel tyrosine kinase gene and the nucleophosmin gene, in accordance with the sequence of the NPM/ALK gene (Morris et al, Science 263:1281, 1994). Meanwhile, the clinicopathologic features of p80-carrying ALCLs have remained unclear. Paraffin sections of 105 cases of ALCL were immunostained using anti-p80 antibody, and 30 of them were shown to express p80. Clinicopathologic comparison between p80-positive and -negative ALCLs showed that p80-positive cases occurred in a far younger patient age group (16.2 +/- 12.9 years; p80-negative cases, 51.0 +/- 22.3 years; P.0001) and the patients showed a far better 5-year survival rate (79.8%; p80-negative group, 32.9%; P.01). These data showed that p80-positive ALCL is a distinct entity both clinically and pathogenetically and should be differentiated from p80-negative ALCL.

Thrombotic thrombocytopenic purpura (TTP) is a rare syndrome of unknown etiology and has a high mortality rate. TTP is characterized by a pentad of clinical findings, including microangiopathic hemolytic anemia, thrombocytopenia, renal abnormalities, neurologic signs and fever. The pathological feature of TTP consists of disseminated microvascular platelet thrombi. We describe a case of TTP with primary anti-phospholipid syndrome. A 27-year-old woman developed TTP in her second trimester of pregnancy. She presented with classical symptoms of TTP with compatible renal biopsy findings. Although four articles of SLE criteria (1982 ARA) were fulfilled, three of them were considered to be derived from multiple thrombosis except for a positive antinuclear antibody. Positive antiphospholipid antibodies (lupus anticoagulant and anticardiolipin antibody) with SLE-like findings suggested the diagnosis of antiphospholipid antibody syndrome rather than SLE. Although TTP has been described in patients with SLE and they can share common clinical and pathological features, the relationship between these two diseases is controversial. Many theories have been proposed to explain the nature and cause of intravascular platelet aggregation in TTP. But the pathogenesis of TTP is still unclear. This case suggests an important causal relationship between antiphospholipid antibodies and TTP during pregnancy. In TTP patients who also have SLE or SLE-like features, the antiphospholipid antibodies may have a role in the development of multiple microthrombosis.

Data concerning HCV infection in Central Brazil are rare. Upon testing 2,350 voluntary blood donors from this region, we found anti-HCV prevalence rates of 2.2% by a second generation ELISA and 1.4% after confirmation by a line immunoassay. Antibodies against core, NS4, and NS5 antigens of HCV were detected in 81.8%, 72.7%, and 57.5%, respectively, of the positive samples in the line immunoassay. HCV viremia was present in 76.6% of the anti-HCV-positive blood donors. A relation was observed between PCR positivity and serum reactivity in recognizing different HCV antigens in the line immunoassay. The majority of the positive donors had history of previous parenteral exposure. While the combination of ALT>50 IU/l and anti-HBc positivity do not appear to be good surrogate markers for HCV infection, the use of both ALT anti-HCV tests is indicated in the screening of Brazilian blood donors.

We evaluated autonomic function in alcoholic neuropathy by non-invasive hemodynamic studies using servo-plethysmo-manometry and laser Doppler flowmetry. In 16 alcoholics compared with 17 age-matched healthy controls, the extent of AP responses to phase IV of the Valsalva maneuver, cold pressor test and isometric exercise decreased significantly, indicating sympathetic hypofunction. Five patients had paradoxical depressor response to cold pressor test, which was reproducible by submersion of the hand in warm water. The data suggest involvement of the higher autonomic center. Reflex bradycardia in phase IV of the Valsalva maneuver and the variation coefficient of R-R intervals in the electrocardiogram were lower, indicating parasympathetic hypofunction. Cutaneous blood flow response in the foot upon local warming and submersion of the hand in cold water was significantly impaired, but that in the contralateral hand was not. Abnormalities in the autonomic function tests may result from a toxic effect of ethanol on the peripheral and central autonomic nervous system and the cardiovascular system. The results indicate not only parasympathetic (vagal) but sympathetic dysfunction mediating cardiovascular regulation in patients with alcoholic neuropathy.

We compared effects of midazolam as intramuscular premedicant on hypnosis, sedation and antegrade amnesia when administered 15 (32 cases) and 30 (35 cases) min before induction of anesthesia. Hypnosis was obtained in 97 and 91%, and sedation in 97 and 100% of patients administered midazolam 15 and 30 min before induction, respectively. Antegrade amnesia was observed in 97 and 72% of patients administered midazolam 15 and 30 min before, respectively (statistically significant). If midazolam is administered 15 min before, the respiratory depression, one of its unacceptable side effects, may hardly occur because patient arrives operating room before its onset. We conclude that the appropriate time for administration of midazolam as intramuscular premedicant is 15 min, rather than 30 min, before the induction of anesthesia.

To investigate the potential role of prostaglandins (PGs) in tubal function in endometriosis.Fallopian tubes were obtained from 36 women undergoing abdominal total hysterectomy.PG production of the human fallopian tube was measured by radioimmunoassay.In normal controls, ampulla and fimbriae in the proliferative and secretory phases produced more PGE and PGF than isthmus. PGE production in ampulla and fimbriae increased in proliferative and secretory phases. PGF production was predominant in the proliferative phase in all parts. There was no significant cyclic or regional variation in 6-keto-PGF1 alpha and thromboxane B2 production.In patients with endometriosis, isthmus and ampulla produced much more PGE and PGF in the proliferative phase than normal controls. The variation of PGF/PGE ratio in endometriosis was different from that of normal controls. It was apparent that tubal PG production is altered in endometriosis.

A case of Nasu-Hakola disease (membranous lipodystrophy) was reported. The patient is a 33-year-old man who started to have pathological fractures at the age of 24 years. Then, neurological symptoms such as dementia appeared gradually. A biopsy specimen of the bone showed membranocystic changes of the adipose tissue. T2-weighted magnetic resonance images of the head showed low intensity in bilateral putamens, internal capsules, globi pallidi and caudate nuclei. One of his brothers has the same disease. In both patients, fatty acid composition of serum total lipids showed increased nervonic acid and plasma amino acid analysis showed decreased glutamine.

Apolipoprotein (apo) E secreted by macrophages plays an important role in nerve injury and repair. We investigated the disturbance of neural apo E metabolism in diabetic rats and its relation to diabetic neuropathy. In BB/W rats, genetically diabetes prone rats, the secretion of apo E from sciatic nerves was 3-fold greater than that in control rats. Furthermore, a similar enhancement of apo E secretion was observed in injured nerves of STZ-induced diabetic rats (2-fold) as compared with those of nondiabetic rats, and this was reversible with insulin treatment. Histological examination of the nerves revealed more extensive infiltration of mononuclear cells in the injured nerves of STZ-induced diabetic rats than in those of non-diabetic rats. This is consistent with the findings that chemotactic activities for mononuclear cells, which were released from injured nerves, were greater in the STZ-induced diabetic rats than in the non-diabetic rats. From these results we conclude that the recruitment of monocyte/macrophages into injured nerves is enhanced in diabetes, thereby causing derangement of neural apo E metabolism. These abnormalities might contribute to the development of diabetic neuropathy.

We applied restriction fragment length polymorphisms (RFLPs) for apolipoprotein (apoAI, apoCIII, apoAIV, apoCI, and apoB) genes to analyze differences between Japanese and Caucasian in allele frequencies as well as those between normal Japanese subjects and patients with coronary artery disease confirmed with coronary arteriography. Although the allelic fragment sizes in the two racial groups showed complete correspondence, the allelic frequencies of these markers detected by the combination of probes and restriction enzymes showed 60% difference in Japanese and Caucasian. There was a significant (p0.01) difference between the normal subjects (with arteriographically-confirmed absence of stenosis in all coronary branches) and those with severe coronary artery disease (50 to 100% stenosis in at least one branch) in plasma levels of apoAI, apoB, total cholesterol, HDL-cholesterol, and LDL-cholesterol. RFLP analysis for 13 markers, however, revealed no significant difference between these groups when analyzed in subjects of all ages (range, 12 to 82 years; N = 306). However, when analysis was restricted to data for 12-to 50-year-olds, a significant (p0.02) difference between the normal control group and the severe coronary artery disease group in 3' apoB probe and EcoRI enzyme test results. An acquired and environmental factors were assumed to be involved in this disease because the correlation between allelic frequencies and coronary artery disease status showed dilution when the subject age distribution included older subjects.

Three cases of malignant histiocytosis were immunohistochemically studied. The cases included the following three patients: a 38-year-old man, a 44-year-old man, and a girl aged 5 years 9 months. All three patients died within 3 months of hospitalization. They had a high fever (temperature over 38.5 degrees C), lymph node swelling, hepatosplenomegaly, and pancytopenia. Blastoid and hemophagocytic cells proliferated in the bone marrow and lymph nodes, especially in the sinuses of the latter. We diagnosed malignant histiocytosis in the three cases based on clinical features, extremely poor prognoses, and the morphologic features and growth pattern of blastoid and hemophagocytic cells. Blastoid and hemophagocytic cells expressed phenotype Mac-387+/KP1+/lysozyme+/polyclonal CD3+. The Mac-387 and KP1 antigens and lysozyme are markers for monocytes/macrophages, and polyclonal CD3 is a marker for T lymphocytes. Therefore, we suggest that a certain number of cases of malignant histiocytosis have a biphenotypic nature, namely, the T cell and macrophage, although many cases of malignant histiocytosis have been reported as expressing only T-lymphocyte antigens.

Uterus origin squamous cell carcinoma cell line LK-52 was established from surgical specimen of lung metastatic nodule. LK-52 produce poorly differentiated squamous carcinoma in nude mouse, and doubling time in vitro was 38 hours. Chromosome analysis show various abnormality and main mode number was 67 and 68. LK-52 shed active procoagulant substance into culture medium. The culture medium of LK-52 shortening recalcification time of normal human plasma and factor VII or factor IX deficient plasma but not factor X deficient plasma. Procoagulant activity of LK-52 product may induced with direct activation of coagulant factor X. Procoagulant activity which produced by cancer cell may play a important roll in the unbalanced haemostasis of cancer patient.

We investigated 9 cases of Ki-1 lymphomas morphologically and immunohistochemically. The lymphoma cells infiltrated in the lymph nodes in 7 cases, in the skin in 6 cases, in both in 4 cases and in the bone marrow in 2 cases. In lymph nodes, the giant tumor cells infiltrated paracortical areas, showing a sheet-like appearance or free cell growth pattern and in the marginal and medullary sinuses as well. In the skin, they formed subcutaneous tumor and infiltrated diffusely also in dermis. All cases were positive for Ber-H2, Ki-1 and HLA-DR and 8 cases revealed some of the T cell phenotypes. But Leu-4 and beta F1 for which all 11 peripheral T cell lymphomas were positive, were only positive in 2 cases, respectively. In the present study, the tumor cells were positive for a few antibodies for T lymphocytes and there were few cases showed positivity for Leu-4 and beta F1. The results suggest that it was questionable whether the tumor cells were derived from T lymphocytes. There may be few cases of Ki-1 lymphomas of distinct T cell lineage.

The immunosuppressive activity of culture supernatants from human T cell leukemia virus type I (HTLV-I)-infected cell lines was examined in vitro. Culture supernatants of both a HTLV-I-infected B cell line, IWS, established from an adult T cell leukemia (ATL) patient and a T cell line, MT-2, suppressed lymphocyte proliferative responses to stimulation with the mitogens phytohemagglutinin (PHA), concanavalin A (Con A), and pokeweed mitogen (PWM). The immunosuppressive factor was not cytotoxic for lymphocytes and did not inhibit the spontaneous growth of ATL cells. It inhibited interleukin-2 (IL-2) production by PHA-stimulated T cells and it arrested PHA-stimulated T cells at the G0/G1 phase of the cell cycle and inhibited entry into the S phase. Furthermore, the factor significantly inhibited the expression of CD3, CD4, and IL-2 receptor (IL-2R) alpha-chain (CD25) on PHA-stimulated T cells. These results suggest that the immunosuppressive factors produced by HTLV-I-infected cell lines might function in the regulation of normal lymphocyte proliferative responses, and that they could play some role in the induction of the immunodeficient condition observed in ATL patients.

Five cases of primary gastric plasmacytoma were studied histopathologically and immunohistochemically. Plasmacytoid cells proliferated diffusely in the propria mucosa, almost preserving the structure of gastric glands. Occasionally, intranuclear inclusions, giant cells, and needle-shaped crystalline inclusions were observed. The neoplastic nature could be suspected on the basis of these histological findings. Immunohistochemically, three cases were positive for IgM and two for IgA. IgM positivity was more commonly observed in the gastric plasmacytoma than in multiple myeloma. Another immunohistochemical study demonstrated that LN-1 negativity and anti-EMA antibody positivity might be an indicator to differentiate gastric plasmacytoma from other types of gastric lymphoma. Four cases of early-stage gastric plasmacytoma have been followed for 5-12 yr. No recurrence has been observed so far. These cases suggest that gastric plasmacytoma has a relatively good prognosis.

The study of the group younger than 29 years of age with pulmonary tuberculosis was carried out. Thirty seven out of 287 tuberculosis patients who were discharged from National Chiba-Higashi Hospital in 1989 were enrolled. Only 5 patients (13.5%) were associated with complication. The smear and culture of sputum for acid-fast bacilli were positive in 30 cases (81.1%) and chest X-ray films revealed cavitary lesion in 31 cases (83.3%). Many of them were moderately advanced cases. Twenty four of them were found symptomatically, 10 by mass survey and 3 under treatment of other diseases. The total delay of symptomatic patients was 8.5 weeks until 80% of them were definitely diagnosed. The days of hospital stay were 122 until half patients were discharged. Five of them (13.5%) were non-Japanese and all stayed in Japan illegally. Their condition was rather severe.

A clinical study of 23 patients with Mycobacterium kansasii infection of the lung encountered at National Chiba Higashi Hospital from 1988 to 1990 was carried out. All 23 cases were male, aged from 25 to 81 years-old. Diagnoses were confirmed by sputum culture. The cases consisted of 15 primary infections and 8 secondary infections. Out of the 23 cases, 11 were detected by mass screening with chest X-ray findings, 10 cases were discovered when visiting the hospital because of chest complications and two cases were diagnosed during the observation of other diseases. On admission, sputum smear examinations were positive for 15 patients and negative for 8 patients. Chest X-ray findings using the roentgenological classification criterion for pulmonary tuberculosis established by the Japanese Society for Tuberculosis, 20 cases revealed a Type II shadow and three cases revealed a Type III shadow. One patient has died from another disease, two are undergoing chemotherapy, two have ceased chemotherapy treatment, and 18 patients have completed the treatment, Sputum cultures rapidly turned to negative for mycobacterium detection after chemotherapy treatment. The prognosis is considered to be quite good.

The influence of renal function on the antihypertensive effect and pharmacokinetics of NZ-105 were studied in 7 patients with essential hypertension (EH) and 6 patients with hypertension having impaired renal function (RH). 1. As for the hypertensive effect, both in EH and RH, the maximum antihypertensive effect was attained 3 to 5 hr after drug administration and there was not significant difference between EH and RH. 2. There was not significant difference in transition of plasma concentration of NZ-105 between EH and RH. 3. Concerning pharmacokinetic parameters of NZ-105, there was significant difference between EH and RH in Tmax. at 20 mg of NZ-105 administration. However, in regard to Tmax. at 30 mg of NZ-105 administration and Cmax., AUC and t1/2 at 20 mg, 30 mg of NZ-105 administration, there were not significant differences between EH and RH. 4. There was no correlation between t1/2 and serum creatinine levels. 5. All cases showed good tolerance without any adverse effect.

During the four-year period from 1987 to 1990, six cases of pulmonary tuberculosis, accompanied by the development of pneumothorax, were observed at our hospital. Distribution by sex was five males and one female. The mean age was 49.8 years-old. None of the patients suffered severe respiratory failure, and there were no deaths in this series. While many of the patients had bilateral exudative disease, five out of the six patients experienced pneumothorax on their right side. The realization of tuberculosis by both patients and doctor tended to be shorter than those cases without pneumothorax.

Cerebral hemodynamics were studied in eight nonpregnant women and 24 women in late pregnancy by internal carotid artery velocimetry with a 3.5-MHz continuous-wave Doppler system. Criteria for supine hypotensive syndrome were a mean blood pressure decrease of 15 mmHg and a 2-minute sustained increase in pulse of 20 beats per minute under postural change from the left lateral to supine position. Nonpregnant and normal pregnant controls not meeting these two criteria displayed decreases of 22.9 and 21.7%, respectively, in time-averaged mean peak velocity (mean velocity) in the supine position compared with the left lateral position. Five subjects with subclinical supine hypotensive syndrome who met one of the above criteria showed a 37.0% decrease in internal carotid artery mean velocity in the supine position. Two patients with supine hypotensive syndrome could not tolerate the supine position for more than 6 minutes, at which time internal carotid artery mean velocity fell below 10 cm/second, reverse flow was observed, and they complained of dizziness, nausea, and syncope. Internal carotid artery mean velocity in all women showed no change in the sitting position compared with the left lateral position. These results indicate that the supine position should be avoided in late pregnancy, especially by women with cerebrovascular complications.

An autopsy case of mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) is reported. It presented with generalized muscle atrophy, stroke-like episodes, schizophrenia-like mental disorder and progressive dementia. Serum lactate and pyruvate levels were high. In the biopsied muscles, ragged-red fibers were observed by light microscopy and aggregation of abnormal mitochondria with paracrystaline formation by electron microscopy. The most characteristic neuropathological findings were infarct-like lesions widespread in the cerebral cortex. In addition, this case showed some unusual pathological features: (1) diffuse moderate fibrillary gliosis in the whole cerebral and cerebellar white matter, which might have been due to metabolic disturbances; (2) several focal lesions with demyelination and numerous spheroids in the pontocerebellar fibers; and (3) marked degeneration of the posterior columns and spinocerebellar tracts. Electron microscopic examination revealed that abnormal mitochondria were markedly aggregated in smooth muscle cells and endothelium of the cerebral and cerebellar blood vessels. These fine structural findings suggest a “mitochondrial angiopathy”.

Both technetium-99m pyrophosphate/thallium-201 dual nuclide SPECT and indium-111 antimyosin antibody/thallium-201 dual nuclide SPECT were performed in identical 11 patients with acute myocardial infarction. Infarct size was calculated by both hot spot imaging agents on dual nuclide SPECT. Antimyosin accurately accumulated in the infarcted area in all 11 patients on SPECT images corresponding with the electrocardiography, but pyrophosphate accumulated at the site of infarct in 10 of 11 patients. The mean volume obtained from pyrophosphate was 32.5 ml and that from antimyosin was 21.9 ml. The relationship between infarct volume calculated by pyrophosphate and that by antimyosin was linear and correlated well (r = 0.98, p less than 0.001). However the volume of infarction determined with pyrophosphate exceeded that with antimyosin SPECT by 1.64 (p less than 0.001). The reason for this difference is not yet known, but may relate to pyrophosphate uptake in border zones that may or may not be irreversibly injured.