Plasma Cell Dyscrasia with Polyneuropathy and Endocrine Disorder: Clinical and Laboratory Features of 109 Reported Cases

We reviewed a series of 109 reported Japanese cases of "plasmacell dyscrasia with polyneuropathy and endocrine disorder."This syndrome shows 1) polyneuropathy with increased proteinlevel in the cerebrospinal fluid and sometimes papilledema,2) endocrinological symptoms, including skin pigmentation, sclerosis,hypertrichosis, gynecomastia, impotence, amenorrhea, decreasedglucose tolerance, edema, pleural effusion and ascites, 3) hepatomegaly,splenomegaly and lymphadenopathy, 4) polycythemia, leukocytosisand thrombocytosis, 5) osteosclerotic changes and 6) plasmacell dyscrasia. Plasma cell dyscrasia is considered to be thecardinal change in this syndrome. Most of the patients havelow levels of IgG. or IgA M-protein in the serum and a slightlyincreased number of plasma cells in the bone marrow. The clinicalcourse is usually chronic. Surgical excision or irradiationof the local lesion and administration of corticosteroids and/oranti-cancer drugs are effective in improving polyneuropathyand other systemic symptoms. This syndrome is apparently morecommon in Japan than in the United States and European countries.The pathogenesis of the association of a variety of symptomsin this syndrome is still unclear.     

How frequent are invasive therapies required in patients receiving tamsulosin for benign prostatic hyperplasia? A retrospective long‐term study

Three hundred Japanese patients with benign prostatic hyperplasia (BPH) who started an alpha1-adrenoceptor blocker, tamsulosin, between 1993 and 1996 were followed for 3.0+/-3.3 years (mean+/-SD) to determine whether an association existed between the disease severities measured prior to the tamsulosin treatment and the timing at which the invasive therapy was implemented. Patients with a lower quality of life (QOL) index or maximum urinary flow rate (Qmax) were transferred for invasive therapy earlier than those with less severe BPH. The International Prostate Symptom Score (I-PSS) was also associated, but apparently to a lesser extent, with the timing of the invasive therapy. Finally, the overall severity evaluated using all of the above three indices, I-PSS, QOL index, and Qmax, in accordance with the 'Severity Criteria for BPH' issued by the Japanese Urological Association, was found to be a good measure for predicting the prognosis of patients with BPH treated with tamsulosin.     

Bisphosphonate induces apoptosis and inhibits pro-osteoclastic gene expression in prostate cancer cells

AIM: Bisphosphonates are well established for the management of cancer-induced skeletal complications. Recent studies suggest that bisphosphonates promote apoptosis of cancer cells as well as osteoclasts in bone metastatic sites. To determine the direct effects of bisphosphonate on prostate cancer, we examined the effects of minodronate on prostatic cancer cell growth and the expression of apoptosis-related proteins and osteoclastogenic factors. METHODS: PC-3, DU145 and LNCaP cells were treated with amino-bisphosphonate minodronate. Then proliferation, apoptosis and expression of bcl-2, bax, poly (ADP)-ribose polymerase (PARP), caspase-3, receptor activator of nuclear factor-kappaB ligand (RANKL), osteoprotegerin (OPG), matrix metalloproteinases-2 (MMP-2), and parathyroid hormone related protein (PTHrP) were assessed. RESULTS: The proliferation of prostatic cancer cells was inhibited by minodronate. DNA fragmentation and TUNEL-positive nuclei were observed in minodronate-treated PC-3 cells. Minodronate decreased bcl-2 expression and induced bax expression, caspase-3 activity and degradation of PARP in DU145 and PC-3 cells. Minodronate decreased expression of RANKL, PTHrP and MMP-2 in PC-3 cells. CONCLUSIONS: Our results suggest that bisphosphonate not only promotes apoptosis directly but also decreases pro-osteoclastic gene expression in prostate cancer cells.     

Immunophenotyping of peripheral blood mononuclear cells collected by cytotoxic and cytotoxic/G-CSF mobilization

We investigated surface immunophenotypes of peripheral blood mononuclear cells (PBMC) collected by cytotoxic and cytotoxic/G-CSF mobilization of peripheral blood stem cells (PBSC) from 38 patients with haematological malignancies in complete remission who underwent consolidation chemotherapy. PBMC were collected by leucapheresis during the haemato poietic recovery phase after intensive chemotherapy. G-CSF was used for mobilization of PBSC in 19 cases. Surface immunophenotyping of frozen-thawed PBMC was performed by flow cytometry. Our findings showed that monocytes and T cells were the two major cell components of PBMC. There were very few B cells in PBMC. Expression of CD45RO and HLA-DR was elevated in lymphocytes, suggesting that T cells in PBMC were activated. The percentage of CD34 positive cells were significantly increased in PBMC collected by cytotoxic/G-CSF mobilization (group 1) compared with PBMC collected by cytotoxic mobil ization (group 2). There were significantly higher percentages of CD14 and CD33 positive cells in group 1 than in group 2. The percentage of CD4 positive lymphocytes positive for HLA-DR was significantly higher in group 1 compared with group 2. These observations indicated that PBMC contained a large number of monocytes and activated T cells, especially in cytotoxic/G-CSF mobilization.     

LONGITUDINAL STUDY OR SERUM THYROID HORMONES, CHORIONIC GONADOTROPHIN AND THYROTROPHIN DURING AND AFTER NORMAL PREGNANCY

Measurements of serum levels of thyroxine (T4), free T4, 3,5,3'-triiodothyronine (T3), free T3, 3,3',5'-triiodothyronine (reverse T3, rT3), thyroxine-binding globulin capacity (TBGcap), chorionic gonadotrophin (hCG) and thyrotrophin (TSH) were carried out prospectively in eight women with uncomplicated pregnancies, in order to examine interrelationships between the thyroid gland and thyroid stimulating hormones during pregnancy. During pregnancy the levels of T4, free T4, T3, rT3 and TBGcap were significantly elevated, and TSH was decreased. It was noted that the elevation of T4 was maintained from the 8th to the 27th week of gestation while the level of TBGcap progressively increased. The levels of free T4 and rT3 in the first and third trimesters were significantly higher than those of age-matched, non-pregnant women. The levels of hCG showed a biphasic variation, with a peak in the 8th to 15th weeks, followed by a decline in the second trimester and a small, secondary elevation in the 32nd to 39th weeks. This later elevation was positively correlated with changes in free T4 and free T3 levels. The increase of serum T4 accompanied by an increase of free T4 in the first trimester appeared due to augmented secretion of T4, rather than being secondary to the elevated levels of TBGcap.     

Abnormal development and differentiation of macrophages and dendritic cells in viable motheaten mutant mice deficient in haematopoietic cell phosphatase

In mice homozygous for the 'viable motheaten' ( me^v ) mutation, numbers of macrophage progenitor cells, particularly monocytes, were markedly increased in the bone marrow and spleen. Increased mobilization of these precursor cells to peripheral tissues and their differentiation to macrophages were evidenced by striking increases in macrophage numbers. Immunohistochemical double staining of tissue sections and flow cytometry analyses of single cell suspensions from these mice demonstrated CD5 (Ly-1)-positive macrophages in the peritoneal cavity, spleen and other tissues. Ly-1-positive macrophage precursor cells were demonstrated in the peritoneal cavity of the me^v mice and developed in the omental milky spots. The development of marginal metallophilic and marginal zone macrophages was poor in the splenic white pulp and related macrophage populations were absent in the other lymphoid tissues. The numbers of epidermal Langerhans cells in the skin and T cell-associated dendritic cells in the thymic medulla, lymph nodes, and the other peripheral lymphoid tissues were decreased. However, increased numbers of dendritic cells accumulated in the lungs, liver, and kidneys. These abnormalities in development and differentiation of macrophages and dendritic cells may be ascribed to the deficiency in haematopoietic cell SHP-1 tyrosine phosphatase or may be a secondary consequence of abnormal microenvironments, (either constitutive or in response to inflammatory stimuli) in the haematopoietic and lymphopoietic organs and tissues of these mice.     

Role of γδ T lymphocytes in the development of Behçet's disease

Phenotypic and functional properties of γδ T cells, which play an important role in mucocutaneous immunity, were examined to elucidate whether immunological abnormality in Behc¸et's disease may be related to a specific T cell population. We found that CD45RA⁺Vγ9⁺Vδ2⁺γδ T cells, which constitute a minor population of γδ T cells in healthy individuals, were increased in number in Behc¸et's disease irrespective of disease activity. This CD45RA⁺ subset of γδ T cells in the active, but not inactive, phase of this disease expressed IL-2Rβ and HLA-DR, suggesting that they are activated in vivo in active Behc¸et's disease. In addition, the CD45RA⁺γδ T cells produced extreme amounts of tumour necrosis factor and contained perforin granules. These data indicate that a phenotypically distinct subset of γδ T cells, CD45RA⁺CD45RO⁻Vγ9⁺Vδ2⁺, may contribute to immunological abnormalities which may lead to complexity of pathophysiology in Behc¸et's disease.     

Acute pericarditis as a result of unusual metastasis of the visceral pleura in a patient with testicular seminoma

A 30-year-old man with a left testicular swelling was referred to our hospital. We performed a left high orchiectomy based on a diagnosis of clinical stage II testicular cancer. Pathological specimens of the left testis showed seminoma. The patient underwent three courses of combined chemotherapy. The retroperitoneal lymph nodes were dissected and there were no viable cancer cells. Twelve years later a right testicular tumor was discovered. The patient underwent a right high orchiectomy. Pathological specimens of the testis showed seminoma, and the patient was treated with prophylactic irradiation. One year after discharge a metastasis was found at a left supraclavicular fossa. The patient was treated with combined chemotherapy and irradiation. Six months after the treatment he complained of dyspnea. We diagnosed the condition as pleuritis carcimatosa. Two days after irradiation to the left thorax the patient suffered a sudden and fatal cardiac arrest. Autopsy survey revealed pericarditis as a result of a direct invasion of visceral pleural metastasis.     

Detection of Philadelphia Chromosome in Chronic Neutrophilic Leukemia

Chronic neutrophilic leukemia (CNL) is a rare myeloproliferativedisorder, differentiated from chronic myelogenous leukemia byseveral features. A case of CNL which was found by long-termculture to involve the Philadelphia chromosome is reported.