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Biomedical subjects

I Sakai

Publications and source records attributed to I Sakai.

At least 55 records · Page 3Linked to original sources

Analgesic effect of a herbal medicine for treatment of primary dysmenorrhea--a double-blind study.

We evaluated the analgesic effect of Toki-shakuyaku-san (TSS) in women who had a combination of "deficiency," of "Yin," "cold," and "stagnated blood" syndromes, and were suffering from dysmenorrhea. A diagnostic scoring system was used for determination of these conditions. We treated patients with either TSS or placebo during 2 menstrual cycles with a double-blind technique, and we followed them for 2 additional cycles. A significant alleviation of dysmenorrhea was observed in patients treated with TSS as compared to those treated with placebo. Our results suggest that TSS is effective for treatment of dysmenorrhea in patients with the above-mentioned conditions.

Adolescent↗

[An autopsy case of Goodpasture syndrome preceded with membranous glomerulonephritis].

Goodpasture syndrome (GS) is an autoimmune disorder characterized by the association of pulmonary hemorrhage and rapidly progressive glomerulonephritis. The pathogenesis of GS is still unknown, but was shown to be the result that antibodies directed against glomerular basement membrane (GBM) antigens could injure both glomerular and pulmonary alveolar basement membrane. And membranous glomerulonephritis (MGN) is a glomerular disease characterized by epimembranous immune deposits and basement membrane thickening. MGN typically presents with the onset of nephrotic syndrome, but it often presents with only asymptomatic proteinuria. We reported an autopsy case of GS preceded with MGN. A 70-year-old man was admitted to our hospital with acute renal failure in May 2, 1996. Percutaneous renal biopsy demonstrated a crescentic glomerulonephritis associated with MGN and linear immunofluorescent staining of the basement membrane with antibodies to IgG. Two weeks later on admission he began to develop slight hemoptysis and chest X-ray showed pulmonary hemorrhage, Furthermore, his serum anti-GBM antibodies titer was very high. He was diagnosed as GS associated with MGN and treated with plasma exchange, glucocorticoid, and cyclophosphamide. Though his symptom was improved for intensive support, he suddenly died on June 22. Autopsied lungs showed focal pulmonary hemorrhage, but were not considered to be life-threatening. The cause of the death remained unclear.

Aged↗

Geranylgeraniol causes a decrease in levels of calreticulin and tyrosine phosphorylation of a 36-kDa protein prior to the appearance of apoptotic features in HL-60 cells.

It was demonstrated recently that geranylgeraniol (GGO) has potent apoptosis-inducing activity in various lines of tumor cells, including HL-60 cells. In the present study, we found that GGO markedly inhibited the expression of a calcium-binding protein, calreticulin, prior to the induction of apoptosis in HL-60 cells. Furthermore, we also observed a significant decrease in the tyrosine phosphorylation of a 36-kDa protein that is a major tyrosine-phosphorylated protein in HL-60 cells. These findings suggest that decreases in levels of calreticulin and in the tyrosine phosphorylation of the 36-kDa protein might be associated with the induction of apoptosis by GGO in HL-60 cells.

Amino Acid Sequence↗

[A case of eosinophilic fasciitis with excessive increase of muscle enzyme].

A sixty-year old woman had muscle pain of her extremities and stiffness in her fingers after unusual physical exertion. On admission she developed indurative swellings of the upper extremities and flexion contractures of her fingers. Laboratory data showed peripheral blood eosinophilia and excessive increase of muscle enzymes. Electromyography showed a myopathic pattern and magnetic resonance imaging showed findings of myositis. We performed a full thickness biopsy from skin to muscle. In histopathologic studies, collagenous hypertrophy of the fascia and perifascicular atrophy of muscle fibers and infiltrates on eosinophiles in the interstitial tissue were found. She was treated with prednisolone (60 mg/day). Clinical symptoms showed improvement and her peripheral blood eosinophiles and serum muscle enzymes deminished quickly. In this case, we suggest that the characteristic histopathologic findings in eosinophilic faciitis is not fascia alone, but includes muscle. We stress that eosinophilic faciitis and polymyositis are closely related.

Anti-Inflammatory Agents↗

[A case of Sjögren's syndrome with lymphocytic interstitial pneumonia].

A 73-year-old woman was admitted to our hospital in January 1995 because of dry cough and dyspnea. A diagnosis of primary Sjögren's syndrome with distal renal tubular acidosis and Hashimoto's disease had been made in 1984. Dry cough developed and a chest X-ray showed bilateral reticulo-nodular shadows in the lower lung field in 1992. Her symptoms had gradually became more severe and the reticulo-nodular shadows on her chest X-ray had spread to both upper lung fields. We performed transbronchial lung biopsy. Biopsy specimens showed lymphocytic infiltration of the aleveolar walls. These lymphocytes were almost CD3-positive and CD19-negative in immunohistopathological studies. CD4-positive cells and CD8-positive cells were present in almost equal numbers. A diagnosis of lymphocytic interstitial pneumonia (LIP) associated with Sjögren's syndrome was made. The patient was treated with prednisolone, 40 mg daily. Her dry cough and dyspnea improved slightly but her chest X-ray remained unchanged. We suggest that immunohistopathological analysis of biopsy specimens may show a difference between lymphocytic infiltration of labial salivary glands and of the lung.

Aged↗

[Acute cardiac failure due to dilated cardiomyopathy in systemic lupus erythematosus with antiphospholipid antibody].

A 33-year-old man presented malar rash in April, 1992. The rash had gradually developed and he was admitted to our hospital in February, 1994. Laboratory findings showed proteinuria of 0.5-0.8 g/ day, thrombocytopenia (4.8 x 10(4)/mm3), false positive serologic test for syphilis, anti-nuclear antibody with a speckled type at a titer of 1 : 80. Activated partial thromboplastin time was prolonged (41.3 s), and anti-beta 2-GPI antibody was strongly positive (56.6 U/ml on enzyme linked immunosorbent assay). The diagnosis of systemic lupus erythematosus with antiphospholipid syndrome was made and prednisolone 60 mg/day improved his manifestations. He could be discharged in July, 1994. Nine months after the discharge he developed dyspnea, and he was admitted to our hospital again. On admission the blood pressure was 212/170 mmHg, Levine III/VI systolic murmur was noted at the apex of heart. Significant laboratory findings showed as follows: WBC 15, 110/mm3 (Neu 73%, Lym 18%), RBC 380 x 10(4)/mm3, Hb 10.2 g/dl, Plt 20.0 x 10(4)/mm3, GOT 23 IU/l, GPT 21.

Acute Disease↗

Signal transduction by a CD16/CD7/Jak2 fusion protein.

The addition of interleukin-3 (IL-3) and granulocyte-macrophage colony-stimulating factor (GM-CSF) to hormone-dependent cells induces tyrosine phosphorylation of Janus protein kinase 2 (Jak2) and activates its in vitro kinase activity. To explore the role of Jak2 in IL-3/GM-CSF-mediated signal transduction, we constructed a CD16/CD7/Jak2 (CD16/Jak2) fusion gene containing the external domain of CD16 and the entire Jak2 molecule and expressed this fusion protein using a recombinant vaccinia virus. The clustering of CD16/Jak2 fusion protein by cross-linking with an anti-CD16 antibody induced autophosphorylation of the fusion protein but did not induce the phosphorylation of either the endogenous Jak2 or the beta chain. Cross-linking of CD16/Jak2 stimulates the tyrosine phosphorylation of a large group of proteins that are also phosphorylated after the addition of IL-3 or GM-CSF and include proteins of 145, 97, 67, 52, and 42 kDa. Closer analysis demonstrated that the CD16/Jak2 phosphorylates Shc, a 52-kDa protein, and the 145-kDa protein associated tightly with Shc, as well as mitogen-associated protein kinase (pp42). Electrophoretic mobility shift assays demonstrate that CD16/Jak2 activates the ability of signal transduction and activation of transcription (STAT) proteins to bind to an interferon-gamma-activated sequence oligonucleotide in a manner similar to that seen after IL-3 treatment. Cross-linking of the CD16/Jak2 protein stimulated increases in c-fos and junB similar to IL-3 but did not cause major changes in the levels of the c-myc message, which normally increases after IL-3 treatment. Thus, a transmembrane CD16/Jak2 fusion is capable of activating protein phosphorylation and mRNA transcription in a manner similar but not identical to hematopoietic growth factors.

Animals↗

Regions of the JAK2 tyrosine kinase required for coupling to the growth hormone receptor.

Growth hormone (GH) treatment of cells promotes activation of JAK2, a GH receptor (GHR)-associated tyrosine kinase. We now explore JAK2 regions required for GHR-induced signaling. Wild-type (WT) JAK2 and JAK2 molecules with deletions of the amino terminus (JAK2ATD), carboxyl terminus (JAK2CTD), or kinase-like domain (JAK2PKD) were each transiently coexpressed in COS-7 cells with the rabbit GHR. The following responses were assayed: GH-induced transactivation of a luciferase reporter governed by a c-fos enhancer element; GH-induced shift in the molecular mass of a cotransfected epitope-tagged extracellular signal-regulated kinase molecule; and GH-induced antiphosphotyrosine immunoprecipitability of the transfected JAK2 form. In each assay, WTJAK2 and JAK2PKD allowed GH-induced signaling, whereas JAK2ATD and JAK2CTD did not. Anti-GHR serum coimmunoprecipitated WTJAK2, JAK2PKD, and JAK2CTD, but not JAK2ATD. Finally, a chimera in which the JAK2 kinase domain replaced the GHR cytoplasmic domain signaled GH-induced transactivation. We conclude: 1) kinase-like domain deletion eliminates neither physical nor functional interaction between JAK2 and the GHR; 2) kinase domain deletion eliminates functional but not physical coupling of JAK2 to the GHR; 3) interaction with the GHR appears dependent on the NH2-terminal one-fifth of JAK2; and 4) a GH-responsive signaling unit can include as little as the GHR external and transmembrane domains and the JAK2 kinase domain.

Amino Acid Sequence↗

The modified method of two-step differential extraction of sperm and vaginal epithelial cell DNA from vaginal fluid mixed with semen.

This investigation was undertaken as an efficient method for isolating sperm DNA from a mixed fluid sample which contains vaginal epithelial cells in a greater amount. The modified method of the two-step differential extraction procedure was found to be suitable for separating sperm DNA and vaginal epithelial cell DNA from the mixed stains. As the first step of digestion, vaginal epithelial cells in the mixed stains were lysed with Proteinase K and SDS, and sperm heads remaining in the lysed solution were collected by centrifugation. As the second step digestion, the sperm heads were lysed with the buffer containing Proteinase K, SDS and DTT as reducing agent. DNA fractions extracted from the two lysed solutions were enriched, one with sperm DNA and the other with vaginal epithelial cell DNA. MCT118(D1S80), ApoB VNTR and HLADQ alpha types of sperm DNA were detected and were confirmed by matching with corresponding male blood DNA. In the case of vaginal secretion mixed with semen of two males, the mixture of MCT118 types of the two males was detected in sperm DNA fraction.

Base Sequence↗

Geranylgeraniol is a potent inducer of apoptosis in tumor cells.

We screened various isoprenoids to find inducers of apoptosis for human leukemia HL-60 cells, and found that GGO (geranylgeraniol) had the most potent apoptosis-inducing activity, as judged from DNA fragmentation in HL-60 cells. The apoptosis-inducing activity of GGO is concentration- and time-dependent. DNA synthesis by HL-60 cells was selectively inhibited on treatment with GGO. Besides HL-60 cells, apoptosis was induced by GGO in various tumor cell lines, including human myeloid multipotential leukemia K562, lymphoblastic leukemia Molt3, and colon adenocarcinoma COLO320 DM.

Adenocarcinoma↗

Novel role of vitamin K2: a potent inducer of differentiation of various human myeloid leukemia cell lines.

When myeloblastic ML1 cells were cultured in the presence of Vitamin K2 (menaquinone, VK2), the population of cells capable of reducing NBT increased to 83.5% at low VK2 concentration of 1 microM, indicating VK2 induces cellular differentiation. VK2 also exerted differentiation-inducing action on histiocytic U937 and promyelocytic HL60 cell lines. None of these effects were observed with Vitamin K1 (phylloquinone, VK1), suggesting the geranylgeranyl group of the side chain of VK2 to be essential to these effects. Combinations of VK2 with other differentiation-inducers such as interferon-gamma, retinoic acid, or camptothecin additively or synergistically induced the differentiation of HL-60 cells. These results suggest that VK2 may safely be used in differentiation therapy in combination with other inducers.

Cell Differentiation↗

[The indications for the use of salazosulfapyridine in rheumatoid arthritis patients].

In an attempt to clarify the background of patients with rheumatoid arthritis (RA) who should be treated with salazosulfapyridine (SASP), a tree classification of responders and non-responders to SASP was developed by analyzing 88 RA patients administered with SASP, according to factors such as clinical findings, autoantibody and HLA antigen. Five clinical features were associated with increased efficacy of SASP: male sex, duration of illness of less than 10 years, initial use of SASP, negative RA test and negative antinuclear antibody. In the tree classification for SASP, there were 3 groups of responders: male sex, female sex + initial use of SASP + negative RA test, and female sex + previous treatment with disease-modifying antirheumatic drugs (DMARDs) +negative antinuclear antibody + negative RA test, while there were 5 groups of non-responders: female sex + previous treatment with DMARDs + negative antinuclear antibody + positive RA test with HLA DR9 or A24 + DR9, and female sex + previous treatment with DMARDs +positive antinuclear antibody with HLA A24, DR9 or A24 + DR9. The new tree classification for the efficacy of SASP in the present study facilitated clear distinction of responders and non-responders to the drug.

Adult↗

Geranylgeranylacetone used as an antiulcer agent is a potent inducer of differentiation of various human myeloid leukemia cell lines.

Low concentrations of geranylgeranylacetone (GGA), known as an antiulcer agent (Teprenone), induces differentiation of various human myeloid leukemia cell lines. The cell lines examined in the present study were myeloblastic ML1, histiocytic U937, promyelocytic HL60, and multipotential K562. All of these cell lines were induced to differentiate by 20 microM GGA, as measured by NBT staining. Neither polyprenylacetones, with more or fewer isoprene units than the geranylgeranyl group, nor polyprenylalcohols had no differentiation-inducing activity. GGA used in combination with RA or TNF-alpha increased ML1 cell differentiation. The present results suggest that GGA may be a useful agent in differentiation therapy of leukemia.

Cell Differentiation↗

Endobronchial involvement with Waldenström's macroglobulinemia.

Although many cases of Waldenström's macroglobulinemia (WMG) with pulmonary involvement have been reported, endobronchial involvement has not been described. We report an unusual case of WMG wherein endobronchial invasion of tumor cells narrowed the airways and caused coughing and wheezing.

Aged↗

[Tubulo-interstitial nephritis (TIN) with no glomerular lesions, distal renal tubular acidosis and asteatosis cutis in a patient with systemic lupus erythematosus (SLE): a case report].

We report a 28-year-old woman with systemic lupus erythematosus (SLE) who showed tubulo-interstitial nephritis (TIN) without any glomerular changes. In 1990, she was admitted to our hospital, complaining of anorexia, vomiting and persistent high fever. Laboratory findings showed proteinuria, pancytopenia, hypocomplementemia and positive for antinuclear antibody, anti-DNA antibody, anti-Sm antibody, anti-SSA antibody and anti-SSB antibody. We made a diagnosis of SLE. Furthermore, distal renal tubular acidosis and asteatosis cutis were revealed. The diagnosis of Sjögren's syndrome was not made. We treated with high-dose prednisolone (60mg/day) and achieved improvement of symptoms and laboratory data. Open renal biopsy showed TIN without any glomerular changes. Predominant TIN is very rare in SLE. We discussed its pathogenesis and relation to the renal lesions of Sjögren's syndrome.

Acidosis, Renal Tubular↗

[Superior sagittal sinus thrombosis following L-asparaginase therapy of acute lymphoblastic leukemia].

A 48-year-old female received serial combination chemotherapy including L-asparaginase (L-ASP) for acute lymphoblastic leukemia. After administration of L-ASP, the prothrombin time and activated partial thromboplastin time were prolonged, while fibrinogen and antithrombin III levels markedly decreased, so she was given fresh frozen plasma (FFP). But subsequently, she developed cerebral infarction in the left parietal region and further hemorrhagic infarction in the right parietal region, and died. Autopsy revealed superior sagittal sinus thrombosis and bilateral cerebral infarction, but no obvious thrombus in other organs. Coagulopathy following L-ASP therapy is well-known. In this case, the coagulation studies at the first attack showed that the plasma protein levels of coagulation and fibrinolysis factors decreased in spite of administration of FFP. Fibrin-fibrinogen degradation products (FDP) slightly increased. However there were no significant abnormalities in the platelet count, nor soluble fibrin monomer, which suggested no evidence of disseminated intravascular coagulation. Thus, these findings suggest that L-ASP might be associated with the pathogenesis of thrombosis in this case.

Antineoplastic Combined Chemotherapy Protocols↗

[Successful treatment of CML in accelerated phase with mithramycin].

The patient, an 18-year-old male, was admitted on May 17, 1988, because of high-grade fever, neuralgia and generalized lymphadenopathy. Bone marrow examination revealed a large number of small nests with myeloid blastic cells negative for both peroxidase and TdT activity. Ph1 chromosome and bcr rearranged fragment were positive. On a diagnosis of CML in the accelerated phase, treatment was started with standard BHAC-DMP and vincristine. However, fever still persisted and hematological improvement could not be obtained. From September 20, 1988, mithramycin was given at 25 micrograms/kg every three days. No fever was noted and the NAP score decreased. However, fever reappeared despite the continuing treatment. Combination use of vincristine (1.0 mg/week) and mithramycin (25 micrograms/kg/week) was then begun, and the fever immediately disappeared. After mithramycin administration, a transient marked increase of neutrophils appeared in the peripheral blood, suggesting the induction of differentiation. After then, a complete remission was obtained. A transient disappearance of Ph1 chromosome by the chemotherapy was noticed. He has remained in the chronic phase of CML for one year. In conclusion, combination use of vincristine and mithramycin may be useful in the treatment of the myeloid blast crisis.

Adolescent↗

[A case of spontaneous regression of malignant lymphoma, complicated with miliary tuberculosis, liver dysfunction and pancytopenia].

An 82-year-old woman was admitted to Iwamizawa Rosai Hospital, Cardiovascular Medicine, for detailed examination of an aneurysm of abdominal aorta. CT scan revealed marked swelling of para-aortic lymph nodes which regressed spontaneously in three months. She was re-admitted to our hospital because of general malaise and gait disturbance. Her chest X-ray on the second admission revealed miliary disseminated shadows, which were confirmed to be tuberculous granuloma by lung biopsy. She was initially well controlled with anti-tuberculosis drugs, followed by severe liver dysfunction and pancytopenia, and died of respiratory and cardiac failure. At autopsy, wide-spread malignant lymphoma and miliary tuberculosis of the lung were found. The cause of liver dysfunction was strongly suspected to be due to infiltration of the lymphoma cells to portal triads of the liver. Hemophagocytosis found in the bone marrow, spleen and liver might be consistent with clinically so-called "hemophagocytic syndrome", causing pancytopenia, associated with infection.

Aged↗