Clinical Implications of t(11;14) in Patients with Multiple Myeloma Undergoing Autologous Stem Cell Transplantation

Conventional cytogenetic analyses and fluorescent in situ hybridization (FISH) are helpful for stratifying patients with multiple myeloma (MM) into high-risk [t(4;14), t(14;16), and/or del 17p] and standard-risk [t(11;14)] categories. However, the prognosis of patients with MM treated with autologous stem cell transplantation (ASCT) stratified according to these categories remains unclear. This retrospective observational study analyzed 97 patients with MM who received a single, planned ASCT after treatment with 200 mg/m² melphalan between 2001 and 2011. The patients were grouped according to chromosomal abnormality, including t(11;14) (n?=?45), t(4;14) (n?=?31), del 17p (n?=?10), t(11;14) with del 17p (n?=?7), and t(4;14) with del 17p (n?=?4). Median overall survival (OS) of the t(11;14) group (64.1 months) was not significantly different from that of the t(4;14) group (not reached), but it was significantly longer than that of the del 17p group (23.0 months; P?=?.002). G-banding revealed that the median OS of the t(11;14) group with additional chromosomal abnormalities (ACAs) (46.2 months) was significantly shorter than that of the t(11;14) group without ACAs (not reached; P?=?.005) and the t(4;14) group (not reached; P?=?.010). These findings highlight the importance of G-banding in patients with t(11;14) MM.     

Oral administration of vitamin C prevents alveolar bone resorption induced by high dietary cholesterol in rats

BACKGROUND: A high-cholesterol diet stimulates alveolar bone resorption, which may be induced via tissue oxidative damage. Vitamin C reduces tissue oxidative damage by neutralizing free radicals and scavenging hydroxyl radicals, and its antioxidant effect may offer the clinical benefit of preventing alveolar bone resorption in cases of hyperlipidemia. We examined whether vitamin C could suppress alveolar bone resorption in rats fed a high-cholesterol diet. METHODS: In this 12-week study, rats were divided into four groups: a control group (fed a regular diet) and three experimental groups (fed a high-cholesterol diet supplemented with 0, 1, or 2 g/l vitamin C). Vitamin C was provided by adding it to the drinking water. The bone mineral density of the alveolar bone was analyzed by microcomputerized tomography. As an index of tissue oxidative damage, the 8-hydroxydeoxyguanosine level in the periodontal tissue was determined using a competitive enzyme-linked immunosorbent assay. RESULTS: Hyperlipidemia, induced by a high-cholesterol diet, decreased rat alveolar bone density and increased the number of tartrate-resistant acid phosphatase-positive osteoclasts. The expression of 8-hydroxydeoxyguanosine was upregulated in the periodontal tissues. Intake of vitamin C reduced the effect of a high-cholesterol diet on alveolar bone density and osteoclast differentiation and decreased periodontal 8-hydroxydeoxyguanosine expression. CONCLUSION: In the rat model, vitamin C suppressed alveolar bone resorption, induced by high dietary cholesterol, by decreasing the oxidative damage of periodontal tissue.     

Cecal Ligation and Puncture Peritonitis Model Shows Decreased Nicotinic Acetylcholine Receptor Numbers in Rat Muscle: Immunopathologic Mechanisms?

Background: Although systemic inflammation is believed to cause upregulation of nicotinic acetylcholine receptors (nAchRs) in muscle, chronic infections such as Chagas' disease occasionally are complicated by myasthenia gravis. The authors investigated how a nonlethal cecal ligation and puncture (CLP) peritonitis model in rats could affect muscle nAchR.

Methods: On day 1, 4, 7, 14, or 21 after CLP or sham operation, nAchR binding was assayed in the anterior tibial muscle and diaphragm using [(125) I] [Greek small letter alpha]-bungarotoxin. The presence or absence of weakness, in vivo dose-response relationships for d-tubocurarine, and serum anti-nAchR antibody titers were assayed in separate experiments.

Results: Systemic inflammation was most severe during the first 4 to 5 days. Numbers of nAchRs were decreased in anterior tibial muscle on days 7, 14, and 21 after CLP, and in the diaphragm on days 7 and 14 (P < 0.01). Both 50% and 90% blocking doses of d-tubocurarine) were lower in CLP rats than in sham-operated rats on days 7, 14, and 21 (P < .05). Weakness was overt in approximately half of CLP rats at these times. Serum anti-nAchR antibody (0.7-1.4 nM) was detectable beginning on day 4 and continuing throughout the 21-day observation period in 58-67% of CLP rats.     

Primary small cell carcinoma of the esophagus with achalasia in a patient in whom pro-gastrin-releasing peptide and neuron-specific enolase levels reflected the clinical course during chemotherapy

We report a case of primary small cell carcinoma of the esophagus in a patient with achalasia in whom pro-gastrin-releasing peptide (ProGRP) and neuron-specific enolase (NSE) levels were measured. Although chemotherapy markedly reduced the size of the primary tumor and lymph node metastases, it had no effect on liver metastases. The tumor marker levels decreased after chemotherapy as the primary tumor and lymph node metastases decreased in size, and they increased as the liver metastases enlarged. However, there was a discrepancy between the levels of ProGRP and NSE during the patient's clinical course. We demonstrate the usfulness of measuring ProGRP and NSE levels to assess the effect of chemotherapy in patients with esophageal small cell carcinoma. Received: April 30, 1998/Accepted: November 27, 1998     

The active digestion of uniparental chloroplast DNA in a single zygote of Chlamydomonas reinhardtii is revealed by using the optical tweezer

The non-Mendelian inheritance of organelle genes is a phenomenon common to almost all eukaryotes, and in the isogamous alga Chlamydomonas reinhardtii, chloroplast (cp) genes are transmitted from the mating type positive (mt(+)) parent. In this study, the preferential disappearance of the fluorescent cp nucleoids of the mating type negative (mt(-)) parent was observed in living young zygotes. To study the change in cpDNA molecules during the preferential disappearance, the cpDNA of mt(+) or mt(-) origin was labeled separately with bacterial aadA gene sequences. Then, a single zygote with or without cp nucleoids was isolated under direct observation by using optical tweezers and investigated by nested PCR analysis of the aadA sequences. This demonstrated that cpDNA molecules are digested completely during the preferential disappearance of mt(-) cp nucleoids within 10 min, whereas mt(+) cpDNA and mitochondrial DNA are protected from the digestion. These results indicate that the non-Mendelian transmission pattern of organelle genes is determined immediately after zygote formation.     

The Long–Evans Cinnamon rat: An animal model for Wilson's disease

The Long-Evans Cinnamon (LEC) rat is known to develop hepatitis and liver cancer spontaneously, phenomena attributed to abnormal copper metabolism. This mutant strain of rat shows some clinical features that are similar to those of Wilson's disease, including excessive copper in the liver, reduced excretion of copper into bile, a reduced level of serum copper and a remarkable decrease in serum ceruloplasmin activity. Molecular studies have revealed that the copper transporting P-type ATPase, atp7b, which is the rat gene homologous to human ATP7B, was found to be defective in the LEC rat. These observations have confirmed that the LEC rat is a rodent model for Wilson's disease. In addition, recent studies have suggested that the ATP7B protein is involved in the intracellular transport of hepatic copper. The absence or diminution of ATP7B function results in abnormal copper metabolism in the LEC rat and in patients with Wilson's disease.     

Binding of human secretory leukocyte protease inhibitor in uterine cervical mucus to immunoglobulins: pathophysiology in immunologic infertility and local immune defense

Objective: To identify an Fc receptor–like molecule in human cervical mucus.

Design: Controlled experimental laboratory study.

Setting: Department of Obstetrics and Gynecology, School of Medicine, University of Tokushima.

Patient(s): Women undergoing treatment for infertility.

Intervention(s): Sodium dodecyl sulfate-polyacrylimide gel electrophoresis and Western blot were used for analysis.

Main Outcome Measure(s): A water-insoluble protein with immunoglobulin-binding activity was purified from human cervical mucus by ammonium sulfate fractionation. The initial 21 amino acids of the N-terminus of the immunoglobulin-binding protein were determined and analyzed in a computer search for homology.

Result(s): The purified fraction contained a 15-kd protein that binds immunoglobulin A, immunoglobulin M, and all subclasses of human immunoglobulin G as determined by Western blot analysis. The amino acid sequence of the N-terminus is identical to that of secretory leukocyte protease inhibitor. The capacity of secretory leukocyte protease inhibitor to bind immunoglobulins was confirmed by Western blot analysis.

Conclusion(s): A component in human cervical mucus capable of binding immunoglobulins was identified as secretory leukocyte protease inhibitor. The capacity to bind immunoglobulins is a unique property of the protein, providing additional support for the contention that it plays an important physiologic role in local tissue defense mechanisms. It also is involved in the pathogenesis of immunologic infertility by trapping sperm in the cervical mucus.     

Attitudes and behaviors of obstetricians and gynecologists toward HPV vaccination: a 7-year follow-up survey in Japan

International Journal of Clinical Oncology - In Japan, the government suspended HPV vaccine recommendation in 2013, resulting in dropping vaccination uptake to almost zero. We conducted four serial...     

Second gas effect of N2O on oxygen uptake

PURPOSE: The concept of the second gas effect is well known, however, there have been no studies that showed the relationship between alveolar oxygen concentration and arterial oxygen tension (PaO2) after the inhalation of nitrous oxide (N2O) in humans. The purpose of this study was to examine the changes in both end-tidal oxygen fraction (F(ET)O2) and PaO2 after N2O inhalation in patients under general anesthesia. METHODS: Fifteen patients scheduled for elective orthopedic surgery were enrolled in this study. Anesthesia was maintained with the continuous infusion of propofol and with nitrogen (N2) and oxygen (O2) (6 L x min(-1), F1O2, 0.33). In all patients, the lungs were ventilated with a Servo 900C ventilator equipped with a gas mixer for O2, N2O, and N2. After obtaining baseline data, N2 was replaced with N2O maintaining FIO2 constant at 0.33. The changes in fractional concentration of O2, N2O, and N2 were continuously measured using mass spectrometer in a breath-by-breath basis. PaO2 and hemodynamic data were obtained at 1, 5, 10, 30 and 60 min after the start of N2O inhalation. RESULTS: Five minutes after N2O inhalation, F(ET)O2 increased from 0.27+/-0.01 to 0.31+/-0.02 (P<0.01) and PaO2 increased from 172.0+/-22.5 mm Hg to 201.0+/-10.3 mm Hg (P<0.01). These effects produced by N2O were observed for 30 min. CONCLUSIONS: These results confirm the concept of second gas effect of N2O on oxygen uptake in humans and provide evidence that the PaO2 increase correlated with the increase in F(ET)O2 after N2O inhalation.     

A case of relapse of C-ANCA-associated glomerulonephritis in post-transplant patients

We experienced a case of relapse of proteinase 3-specific antineutrophil cytoplasmic autoantibody (C-ANCA)-associated rapid progressive glomerulonephritis (RPGN) in a patient after renal transplantation. A 19-yr-old man, who underwent a living donor kidney transplantation, presented a rapid renal function deterioration along with a sign of infection. Initially he was treated as acute rejection, but renal function did not improve. Renal biopsy revealed crescentic glomerulonephritis, and C-ANCA titer was 12 EU/mL, resulting in the diagnosis of C-ANCA-associated RPGN. He was treated with three consecutive methylprednisolone pulses twice in addition to the basal immunosuppressive medications (cyclosporine A and mizoribine), then his renal function improved to normal. Bearing the possibility of recurrence of glomerulonephritis in mind, we re-evaluated the nature and disease course of renal failure of original kidney. He experienced a rapid deterioration of renal function in 1992, and eventually CAPD was started in 1992. His serum in 1992 revealed high titer of C-ANCA (24 EU/mL), and renal biopsy performed in 1992 showed a crescentic glomerulonephritis. Taken together, we diagnosed this event as a relapse of C-ANCA-associated GN. Lessons from our experience are: 1) steroid pulse and high-dose corticosteroid therapy may be useful for the treatment of relapse of C-ANCA-associated GN patients after renal transplantation; 2) the possibility of a relapse of C-ANCA-associated GN following renal transplantation has to be kept in mind, especially when infection precedes the deterioration of allograft kidney function.