The pilot trial of the prevention of the increase in electrical taste thresholds by zinc containing fluid infusion during chemotherapy to treat primary lung cancer.

It is well known that there are various adverse effects during chemotherapy for cancer treatment. A taste disorder is also seen in 35-70% of patients. It has been reported that a zinc deficiency is associated with the development of these alterations in taste sensation. The purpose of this pilot study was to determine whether the zinc including infusion had the effect on taste disorder in patients with lung cancer. Taste disorder was evaluated as the increase in electrical taste thresholds using an electrogustometer. The plasma zinc concentration was also measured. Although there was no significant correlation, the increase in taste thresholds was detected in many patients who had a low zinc concentration even before receiving chemotherapy. Moreover, after 2 weeks of chemotherapy, almost all patients who did not have a zinc containing infusion showed development of taste disorder (5/5, 100% at chorda tympani area; 4/5, 80% at glossopharyngeal area), whereas no development of taste disorder was observed in those patients receiving a zinc containing infusion. These results suggest the possibility that the administration of zinc during chemotherapy could be a useful supportive therapy for preventing taste disorder and to help maintain a better quality of life.

Effect of coffee consumption on bone metabolism.

The effects of coffee on bone metabolism are still controversial, although several studies have suggested that caffeine and/or heavy coffee consumption is associated with a significant increase in risk of fracture, osteoporosis, and periodontal disease. Therefore, we sought to clarify the relationship between coffee consumption and bone metabolism using male Wistar rats. Forty-eight male Wistar rats were assigned to three treatment groups including a control-diet group (control, n = 16, coffee-free diet), a 0.62% coffee-diet group (low caffeine, n = 16, diet supplemented with 6.2 g/kg of the control diet), and a 1.36% coffee-diet group (high caffeine, n = 16, diet supplemented with 13.6 g/kg of the control diet), and animals were maintained on an experimental diet for 140 days. Although caffeine in serum was not detected in rats fed the control diet, low-intake coffee for 140 days led to an increase in caffeine concentration to 0.53 +/- 0.11 microg/mL and high-intake coffee led to an increase of 1.77 +/- 0.22 microg/mL. No significant differences in body weight change, serum and urinary biochemical markers of bone metabolism, and bone histomorphometry were found between the coffee-diet groups and the control-diet group, except that urinary phosphorus excretion after 140 days of both coffee diets was significantly increased compared with controls (p < 0.05). In addition, the coffee diets were not associated with differences in tumor necrosis factor-alpha and interleukin-6, which have been implicated in the pathogenesis of bone loss together with interleukin-1beta. In conclusion, the present study strongly indicates that coffee does not stimulate bone loss in rats.

Long-term local hyperthermia in the treatment of advanced breast cancer (case report).

BACKGROUND: It is difficult to control non-resectable locally advanced primary and recurrent breast cancer by conventional modalities. Recently, hyperthermia (HT) has been recognized as an effective adjuvant to radiotherapy (RT) and chemotherapy (CT) in treatment of various malignancies, including breast cancer. PATIENT AND METHODS: The patient was a 58-year-old female Japanese, with breast cancer, T4N2M0, stage IIIb (papillo-tubular carcinoma). Previous treatment included RT and neoadjuvant CT Local HT was performed with a total number of 87 sessions given over 12 months. The mean time of each session was 40 minutes. Elevation of temperature to a tumoricidal level of 43 degrees C was confirmed. The patient received cyclophosphamide (50 mg p.o./day) and tamoxifen (20 mg p.o./day) during the whole period of HT. Due to the decreased amount of WBC, further CT was not possible, except for one course of CMF performed 3 months after the start of HT. RESULTS: The patient had a decrease in the intensity of pain even after the first 3 sessions. In one month, movement in the right shoulder became possible in an anterio-posterior direction. By 5 months, the healing of ulceration became evident. At present, the patient is in continuous CR for 15 months after HT. The movement in the shoulder joint is markedly improved in all directions. In addition, HT did not cause any notable complications. CONCLUSION: Long-term HT may be useful in the management of locally advanced breast cancer and these results should encourage further clinical study.

Massive gastrointestinal hemorrhage in a case of amyloidosis secondary to rheumatoid arthritis.

A case of a 60-year-old woman with secondary gastrointestinal amyloidosis to rheumatoid arthritis is reported. Biopsy findings in the mucosa of the stomach and lower gastrointestinal tract revealed amyloidosis. Endoscopic examination of the lower gastrointestinal tract revealed multiple nodular elevations. The patient showed massive melena. Emergency angiography was performed and an extravasation was found at branches of the jejunal artery. Embolization was performed and this lead to a good prognosis. Patients with massive hemorrhages following gastrointestinal amyloidosis generally have a poorer prognosis. Embolotherapy performed for the present case might represent an effective therapeutic method for gastrointestinal hemorrhage in gastrointestinal amyloidosis.

Vitamin E treatment of experimental glomerular disease in rats.

BACKGROUND: Kidney mesangial cells (MCs) and vascular smooth muscle cells (VSMCs) are closely related in terms of origin, microscopic anatomy, histochemistry, and contractility. This relationship suggests a similarity between kidney glomerular sclerosis and atherosclerosis. Vitamin E appears beneficial in the prevention and treatment of coronary heart disease and it also inhibits the proliferation of VSMCs in vitro. Thus, we investigated the effect of vitamin E on glomerular sclerosis and MC-proliferative glomerulonephritis (GN) in two rat models of glomerular disease. METHODS: A remnant kidney rat model accelerated with hyperlipidemia was used to examine progressive glomerular sclerosis leading to chronic renal failure. A rat model of MC-proliferative GN was induced by the intravenous administration of absorbed rabbit anti-rat thymocyte serum (ATS). RESULTS: In the remnant kidney rat model, dietary supplementation with vitamin E (500 IU dl-alpha-tocopheryl acetate/kg) and cholesterol (2%) significantly inhibited glomerular sclerosis and macrophage infiltration in glomeruli relative to controls receiving basal and cholesterol-supplemented diets. In the ATS-induced GN model, glomerular cell proliferation (principally MCs) was lower in rats fed diets supplemented with vitamin E (1000 IU dl-alpha-tocopheryl acetate/kg) compared with controls fed the basal diet only. Although the degree of glomerular macrophage infiltration was similar in both groups, fewer proliferative cell nuclear antigen (PCNA)-positive cells were observed in the vitamin E group, suggesting that MC proliferation was suppressed via the inhibition of intracellular transduction. CONCLUSIONS: Supplemental dietary vitamin E suppresses MC proliferation and glomerular sclerosis in models of glomerular disease in rats. This action of vitamin E in experimental nephritis suggests the value of clinical trials testing the potential benefit of vitamin E in chronic GN patients.

Effect of vitamin E on lipid metabolism and atherosclerosis in ESRD patients.

BACKGROUND: Oxidative stress is enhanced in patients with end-stage renal disease (ESRD) undergoing hemodialysis (HD). Bioincompatibility represents an important source of reactive oxygen species. HD patients exhibit altered anti-oxidative defences and anti-oxidative vitamins such as vitamin E and C are altered in uremia. Frequently, HD patients also suffer from atherosclerotic cardiac disease. We have previously reported that low density lipoprotein (LDL) of HD patients is rich in malondialdehyde (MDA), an end product of lipid peroxidation. MDA rich LDL is thought to be an atherogenic lipoprotein due to its enhancement of macrophage foam cell formation. METHODS: We conducted a controlled study for two years comparing the effects of a vitamin E coated cellulose membrane dialyzer and an ordinary cellulose membrane dialyzer on lipid metabolism and the progress of atherosclerosis. LDL-MDA and oxidized LDL (ox-LDL) were measured in HD patients using these two types of dialyzers. Plasma vitamin E and lipid concentrations were also evaluated. The aortic calcification index (ACI) was evaluated by CT scan to assess the progress of atherosclerosis before and for every year after treatment. RESULTS: Use of a vitamin E coated cellulose membrane dialyzer for six months, one year and two years resulted in a significant reduction in LDL-MDA and ox-LDL compared to the ordinary cellulose membrane dialyzer. Treatment with a vitamin E-coated dialyzer significantly reduced the percentage increase in ACI after 24 months compared to the control. There were no significant changes in plasma vitamin E and lipid concentrations between the two groups. CONCLUSIONS: These results suggest that the oxidative stress could be one of the stimulating factors of abnormal lipid metabolism and atherosclerosis in ESRD patients.

Factors associated with calcification of the abdominal aorta in hemodialysis patients.

BACKGROUND: Cardiovascular and cerebrovascular injury caused by arteriosclerosis has been the major cause of the death in hemodialysis (HD) patients. We quantitatively analyzed and evaluated the severity of abdominal aortic calcification in HD patients in comparison to risk factors for arteriosclerosis. METHODS: One hundred thirty-seven HD patients were examined. Using image analysis software, areas of the calcified abdominal aorta were quantitatively analyzed on plain computerized tomography images. Other factors such as blood pressure (BP), lipid levels, and calcium (Ca) x phosphorus (Pi) value were also analyzed. RESULTS: Patients with a higher one-year average of systolic BP showed a higher severity of abdominal aortic calcification. That is, the severity of abdominal aortic calcification in patients with a one-year systolic BP average above 160 mm Hg was 31.5 +/- 13.6%, and this severity was significantly higher than that in patients with a one-year systolic BP average of less than 120 mm Hg (8.0 +/- 7.7%, P < 0.01). The severity of abdominal aortic calcification in patients demonstrating risk values of ectopic calcification, that is serum Ca x Pi > or = 60 (mg/dl), on more than 4 of 24 measurements within one year (25.8 +/- 13.6%) was significantly higher than the severity of aortic calcification in patients demonstrating this value less than four times in one year (P < 0.05). There was no correlation between levels of low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglyceride, lipoprotein(a), and severity of abdominal aortic calcification. CONCLUSIONS: Systolic BP levels and the product of serum Ca and Pi were related to the severity of abdominal aortic calcification in HD patients. These observations suggested that BP control, as well as control of serum Ca and Pi levels, was important in preventing the progression of abdominal aortic arteriosclerosis.

Phosphotyrosine of macrophage by low-density lipoproteins from hemodialysis patients.

BACKGROUND: Because of the possible importance of tyrosine phosphorylation in the signal transduction process, we investigated whether an interaction of low-density lipoprotein (LDL) from hemodialysis patients (HD-LDL) and human macrophages induces tyrosine-phosphorylated proteins in the macrophages. METHODS: Human monocyte-derived macrophages were incubated with HD-LDL (100 micrograms/ml) or native LDL (100 micrograms/ml) for 15 minutes at 37 degrees C. Whole cells were lyzed with Tris-HCl buffer containing vanadate and Triton X-100. After centrifugation, lyzed proteins were divided into Triton-soluble and -insoluble fractions. Both fractions (soluble and insoluble) were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and were electroblotted onto a polyvinylidene difluoride (PVDF) membrane. Immunoblotting was performed using an antibody against phosphotyrosine or c-Src. RESULTS: Several proteins in the range 40 to 100 kDa were found to be phosphorylated constitutively in the macrophages and not affected by the addition of HD-LDL. HD-LDL did not induce any tyrosine-phosphorylated proteins either in the soluble or insoluble fractions. Macrophages pretreated with tyrosine kinase inhibitor genestein drastically inhibited tyrosine phosphorylation of these proteins. The nonreceptor tyrosine kinase, c-Src p60, was also strongly tyrosine phosphorylated in the macrophages, and this was not enhanced by the stimulation of HD-LDL. CONCLUSION: These data suggest that tyrosine autophosphorylated proteins may play a role in the early step of signal transduction in the macrophages.

[Primary pulmonary cryptococcosis with pleural effusion].

A 32-year woman presented at our hospital with left chest pain. Chest X-ray films revealed multiple nodular shadows (accompanied by a fusing tendency) and pleural effusion in the left lower lung field. Transbronchial lung biopsy specimens contained cryptococcal fungi. Blood and pleural effusion samples were positive for cryptococcal antigen, but cerebrospinal fluid was not. Because cryptococcus was not detected in cultures of cerebrospinal fluid, urine, or blood, and because the patient had no underlying disease, she was given a diagnosis of primary pulmonary cryptococcosis. On the second consultation 10 days later, the patient's subjective symptoms had subsided and the X-ray findings were generally improved. The condition resolved spontaneously without treatment within 4.5 months. This case is noteworthy for several reasons: (1) pleural effusion was observed, and the fluid could be examined: (2) the inflammatory reactions were pronounced at the time of first examination; and (3) the disease developed abruptly but subsided spontaneously within a short period of time. We reviewed 15 cases of primary pulmonary cryptococcosis reported recently in this journal, including this case. That review suggests that the finding concerning inflammatory reactions are associated with the motive of detection during initial examination.

Inhibition of macrophage migration inhibitory factor secretion from macrophages by vitamin E.

Macrophage migration inhibitory factor (MIF) was identified in rat peritoneal macrophages by Western blot analysis and its secretion into culture medium by enzyme-linked immunosorbent assay. We investigated the effect of vitamin E on MIF production in macrophages in response to phorbol 12-myristate-13-acetate (PMA), calcium ionophore A23187, and lipopolysaccharide (LPS). Intraperitoneal injections of vitamin E (5 mg per rat) for 6 successive days resulted in a significant increase of alpha-tocopherol content in peritoneal macrophages (478.3+/-90.7 ng/106 cells) compared with the control (1.5+/-0.5 ng/10(6) cells). For the control macrophages, MIF content of the medium (2.5x10(6) cells/18 ml) without stimulation was 2.27+/-0.20 ng/ml after 14 h culture, whereas stimulation with calcium ionophore A23187 (400 nM) and LPS (5.0 microg/ml) induced the elevation of MIF content to 3. 66+/-0.41 and 4.12+/-0.58 ng/ml, respectively. On the other hand, vitamin E-enriched macrophages without stimulation showed less MIF content (0.77+/-0.23 ng/ml) than the control. Similarly, the increase of MIF of vitamin E-treated macrophages was significantly suppressed after stimulation with calcium ionophore A23187 or LPS, compared with the control macrophages. From analysis of intracellular MIF content by Western blot, we found no alteration of intracellular MIF content of vitamin E-macrophages, in contrast to the decreased content of control stimulated-macrophages. Taken together, these results indicate that vitamin E may contribute to the regulation of immune responses through regulation of MIF secretion.

A truncated species of apolipoprotein B (B-38.7) in a patient with homozygous hypobetalipoproteinemia associated with diabetes mellitus.

Familial hypobetalipoproteinemia is caused by mutations in the apolipoprotein (apo) B gene. We identified a 57-year-old woman whose plasma total cholesterol and apoB levels were 2.17 mmol/L and 0.03 g/L, respectively. Separation of plasma lipoproteins by sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed the absence of apoB-100 and the presence of a faster-migrating form of apoB with an apparent Mr of 195 kDa. Direct sequencing of a polymerase chain reaction-amplified fragment of the patient's apoB gene DNA revealed a single C-->T transition at nucleotide 5472 that converts glutamine 1755 (CAA) to a stop codon (TAA). We predict this novel nonsense mutation of the apoB gene to produce a truncated protein that contains 1754 amino-terminal amino acid residues of apoB-100. We designated this mutant form of apoB apoB-38.7 by following the centile nomenclature of the apoB species. The same mutation was found in both of her children. The proband revealed clinical findings of retinitis pigmentosa, acanthocytosis, and loss of deep tendon reflexes that are characteristic of severe hypobetalipoproteinemia. In addition, the proband had type II diabetes mellitus with nephropathy, anemia, cholelithiasis, hepatic hemangioma, bronchiectasis, and extensive calcification of major arteries including, the celiac, splenic, and renal. In summary, we have found a novel truncated apoB, apoB-38.7, in a patient with an unusual presentation of hypobetalipoproteinemia that includes diabetes mellitus and extensive arterial calcification.

Successful immunochemotherapy for patients with malignant mesothelioma: report of two cases.

Malignant mesothelioma is a clinically aggressive tumor and has a poor prognosis; therefore, the selection of therapeutic strategies is important to improve the prognosis. Two patients with intraperitoneal malignant mesothelioma received combination therapy as follows: (1) case-oriented chemotherapy according to the results of a chemosensitivity test, and (2) adoptive immunotherapy using cytotoxic T lymphocytes (CTL). The chemosensitivity test was assessed by an MTT colorimetric assay. CTL was generated by a mixed culture with autologous tumor cells, and activated by immobilized anti-CD3 monoclonal antibody and interleukin-2. The MTT assay indicated that cisplatin and adriamycin were sensitive drugs in both patients, and they thus received the case-oriented chemotherapy according to the MTT assay. The activated CTL exhibited a high cytotoxicity against autologous malignant mesothelioma cells, and were transferred intraperitoneally. The patients were controllable for ascites, and the tumor masses gradually vanished (partial response). Chemoimmunotherapy is thus considered to be an effective treatment for intraperitoneal malignant mesothelioma, especially to improve the quality of life.

[Two cases of anti-neutrophil cytoplasmic antibody-negative generalized Wegener's granulomatosis with alveolar hemorrhage].

Anti-neutrophil cytoplasmic antibody (ANCA) is a distinct marker for Wegener's granulomatosis. We report two cases of ANCA-negative Wegener's granulomatosis. A 70-year-old woman (case 1) and a 27-year-old woman (case 2), who had sinus symptoms and renal disorders, were admitted to our hospital with alveolar hemorrhage. Wegener's granulomatosis was diagnosed on biopsy of the nasal mucosa. Case 1 responded well to the combination therapy with cyclophosphamide and prednisolone, while case 2 responded well to pulse therapy with methyl-prednisolone. These findings suggest that patients with ANCA-negative Wegener's granulomatosis may respond well to chemotherapy. This might lead to an improved prognosis in even severe cases, even though the prognosis of generalized Wegener's granulomatosis with alveolar hemorrhage is usually poor.

[Squamous cell lung cancer with minimal-change nephrotic syndrome].

We report a case of squamous cell lung cancer with nephrotic syndrome. A 69-year-old man was admitted because of proteinuria and microhematuria. A plain chest X-ray film on admission showed a large mass in the left-lower lung field. The patient was given a diagnosis of minimal-change-nephrotic syndrome and squamous cell lung cancer. We first treated the nephrotic syndrome with glucocorticoid therapy, and then treated the lung cancer with chemo-radiotherapy. This reduced the lung cancer, alleviated the proteinuria, and completely resolved the nephrotic syndrome. Nephrotic syndrome is generally associated with malignant lymphoma and other nonepithelial neoplasms. As the underlying disease, epithelial neoplasms are less common, but lung cancer is one of the most widely reported. Histologically, most cases of cancer-associated nephrotic syndrome exhibit membranous nephropathy; Minimal-change nephrotic syndrome is rare. Deposits of immunocomplex on glomerular basement membrane are considered to play a pathogenic role in membranous nephropathy. However, the pathogenesis of minimal-change nephrotic syndrome is different.

Increased expression of a brain/embryo-type myosin heavy chain isoform (MIIB2) in mesangial proliferative glomerulonephritis.

Proliferation of mesangial cells is frequently found in glomerulonephritis, such as IgA glomerulonephritis. Recent reports suggest that a brain/embryo-type myosin isoform (MIIB2) is involved in cell proliferation. We have studied the expression of MIIB2 in renal biopsy samples from patients with various renal diseases and in the renal tissues from the rat model of mesangial proliferative glomerulonephritis induced with anti-Thy 1.1 antibody. Immunohistochemical analysis of the biopsy samples using an anti-brain-type myosin heavy chain-specific monoclonal antibody (HBM1) indicated that 92% of the samples from patients with IgA glomerulonephritis contained a significant population of mesangial cells that reacted with the antibody. Most of the samples from patients with other types of proliferative glomerular diseases also contained HBM1-reactive mesangial cells, while none of the samples from patients with non-proliferative glomerular diseases contained a significant population of HBM1-reactive mesangial cells. The expression of a brain/embryo-type myosin heavy chain isoform (MIIB2) in the mesangial cells began at five days after injection of anti-Thy 1.1 antibody and peaked at the tenth day. On the other hand, the expression of the proliferating cell nuclear antigen in the mesangial cells was induced at two days after injection of anti-Thy 1.1 antibody and was maximal at the fourth day. These results indicate that the expression of the MIIB2 isoform by mesangial cells is accelerated in proliferative glomerulonephritis and suggest that the myosin isoform is involved in the phenotypic transformations of the glomerular tissues rather than in the cell proliferation.

[A case of malignant rheumatoid arthritis with lupus anticoagulant and cerebral infarction].

We reported a case of malignant rheumatoid arthritis (MRA) with cerebral infarction associated with a possible cause of lupus anticoagulant. The patient was a 68-year-old woman who had received treatment for rheumatoid arthritis (RA) from 15 to 16 years ago. She consulted to our hospital with a major complaint of right hemiplegia. Brain CT revealed a low density area in the left hemisphere. She was diagnosed as cerebral infarction and hospitalized. Since she was noted to have hypocomplementemia, interstitial pneumonia and pericarditis, she was diagnosed as MRA. Coagulation test disclosed positive lupus anticoagulant (LA). Generally, CNS disorders in MRA are uncommon. Cerebral infarction was complicated in the present case, suggesting the involvement of antiphospholipid antibodies as its pathogenesis.

Effect of alpha-tocopherol on in vitro and in vivo metabolism of low-density lipoproteins in haemodialysis patients.

It has been reported that some modified low-density lipoproteins (LDLs) such as glycated LDL and malondialdehyde-rich LDL (MDA-LDL) probably exist in the circulation. The present study was undertaken to investigate the in vitro and in vivo metabolism of MDA-LDL occurring in chronic haemodialysis patients and the effects of alpha-tocopherol on these abnormalities. MDA-LDL from haemodialysis patients was degraded more rapidly by human monocyte-derived macrophages and disappeared more slowly from the circulation when compared with LDL from healthy controls. Treatment with alpha-tocopherol at doses of 600 mg/day for 2 weeks resulted in improvement of these metabolic abnormalities depending upon the degree of return to normal MDA concentrations in LDL.