Sequence analysis of two serological variants, HLA-A2K and HLA-A9HH, detected in Japanese

Two rare variants of HLA-A locus antigens, tentatively called HLA-A2K and HLA-A9HH, were serologically identified in the Japanese population. A2K and A9HH showed short reaction patterns of a series of anti-A2 and anti-A9 sera, respectively. The latter variant also reacted with some anti-A2 sera. Nucleotide sequences of full-length cDNAs for A2K and A9HH were determined. The results revealed that both antigens are encoded by previously undescribed alleles. The nucleotide sequence of the allele for A2K was identical to that of A^*0207 except for a single nucleotide difference in exon 3. The nucleotide sequence of the allele for A9HH was identical to that of A^*2402 except for two nucleotides in exon 2. These two nucleotides are shared by all the reported A2 alleles. These sequencing results the allele for A9HH were consistent with the serological cross-reactivity of A9HH with some anti-A2 sera.     

Study of monoclonal gammopathy in Kagawa Prefectural Central Hospital

We investigated 361 patients with monoclonal gammopathy in whom immunoelectrophoresis was performed (1,037 tests) between 1986 and 2002 at Kagawa Prefectural Central Hospital. In this study, we identified 222 patients with monoclonal gammopathy of undetermined significance (MGUS). Malignant transformation of MGUS to multiple myeloma occurred in 15 patients (6.8%). No significant differences were observed in the means of total protein (TP), albumin (Alb), albumin/globulin ratio (A/G ratio), IgG, IgA, or IgM level in the initial examination between the patients who remained as MGUS and patients with malignant transformation of MGUS. However, the rate of progression to malignancy was high when the levels of normal immunoglobulins other than M protein were below the normal range. Since the number of MGUS cases detected and the number of protein fractionation performed were proportionate, and MGUS was found by protein fractionation in routine tests, protein fractionation is essential for detection of MGUS, and it is necessary to add serum protein fractionation to routine initial examination. In addition, long-term follow-up of patients with monoclonal gammopathy and preparation of a database of patient information are useful for monitoring the outcome.     

FLUORESCENCE AND ELECTRON MICROSCOPIC STUDIES ON THE PERIVASCULAR MESENCHYMAL CELLS AND FIBROBLASTS AFTER VITAMIN A ADMINISTRATION

Findings of perivascular mesenchymal cells and fibroblasts in mice receiving large doses of vitamin A were described. Liver, lung, intestine and skin were investigated by fluorescence and electron microscopy. Marked increase of fluorescence of vitamin A was observed in the sinusoidal wall of the liver, in the alveolar septa of the lungs, in the propria mucosa, submucosa and muscular layer of the intestine and in the dermis of the abdominal skin. Increased fluorescence of these organs corresponded, ultrastructually, to the appearance of numerous fat droplets in Ito cells of the liver, septal cells of the lung and fibroblasts of the intestine and of the skin. All of these cells showed the same morphological features and the same distribution in the tissue, namely in the interstitial connective tissue space. These findings indicate that vitamin A storing cells are distributed widely in the connective tissue of various organs and that perivascular vitamin A storing mesenchymal cells and interstitial fibroblasts are probably of common fibroblastic cell line.     

Clinical features of oral allergy syndrome to plant foods allergens in Kanto regions]

BACKGROUND: Recently, it is recognized that the patients of oral allergy syndrome (OAS) to fruits are increasing. However, there are little knowledges of the background, character, and seriousness about these patients in Kanto regions. OBJECTIVE: We aimed to investigate the clinical features of OAS patients to plant origin foods in Kanto regions. METHODS: The patient, who visited Sagamihara National Hospital from 2000 to 2005 and developed some allergic symptoms to plant origin foods, were studied by a questionary survey. RESULTS: As for the 42 subjects, average age are 36 years old, male:female=8:34, merger of other allergic disease is 35 allergic rhinitis of 42 subjects (83%), 34 of asthma (81%), 14 of atopic dermatitis (33%). The causes of OAS symptoms are 32 rose-family fruits, 34 non-rose family fruits, 14 vegetables, 11 nuts, 2 grains subjects. As for the symptom, only in the oral and pharynx symptoms are found in 12, the systemic symptoms is 29, anaphylaxis is 11 subjects. Allergic rhinitis preceded on the 90% subjects with pollinosis, very high rate. On the other hand, the 20% of all subjects have no symptoms of allergic rhinitis. CONCLUSION: A nasal catarrh symptoms went ahead in most of the OAS subjects in Kanto regions. In addition, considering from some patients have no black alder pollinosis and/or are allergic to many non-rose-family fruits at high frequency, there might be a broad cross-reactivity between many pollens other than alder and plant origin foods.     

Inhibitory effect of oral administration of Lactobacillus casei on 3-methylcholanthrene-induced carcinogenesis in mice

The present study was designed to determine whether tumor induction by 3-methylcholanthrene (MC), a carcinogenic hydrocarbon, can be inhibited by oral administration of Lactobacillus casei strain Shirota (LC). C3H/HeN mice were divided into four groups and assigned to the following treatments: treated with MC and given control or LC-containing diet; treated with vehicle only and given control or LC-containing diet. MC (1 mg) was injected intradermally at 7 weeks of age and the tumor incidence was monitored; LC was mixed into a diet at a concentration of 0.05% (w/w) and the diet was fed from the day of MC injection throughout the study. Spleen cells were analyzed for the immune parameters at 12 and 16 weeks after the MC injection. Oral feeding of mice with LC reduced tumor incidence (P < 0.05). MC treatment lowered the in vitro response to concanavalin A (Con A) of spleen cells, the secretion of interleukin-2 in spleen cell culture after stimulation of the cells with Con A and the proportions of CD3⁺, CD4⁺ and CD8⁺ splenic cells. However, the analysis of the spleen cells obtained from the mice treated with MC and given the LC-containing diet revealed that these disrupted host immune parameters were maintained at the level of normal controls. These results suggest that oral feeding of mice with LC inhibits MC-induced tumorigenesis by modulating the disrupted host immune responses during MC carcinogenesis. Received: 14 April 1999     

Pulmonary hypertension due to tumor emboli: A report of three autopsy cases with morphological correlations to radiological findings

Three cases of pulmonary hypertension caused by tumor emboli to the lungs are described. Two of the three cases had a clinical diagnosis of pulmonary thromboembolism until surgical embolectomy, and the other had a diagnosis of primary pulmonary hypertension. Autopsy disclosed chondrosarcoma, choriocarcinoma and gastric cancer as the primary tumors, respectively. Pulmonary vascular obstruction due to tumor embolism leading to pulmonary hypertension is a previously rare clinical entity, and obstructed pulmonary vessels are believed to tend to be small vessels. We compared the autopsy and radiological findings and concluded that pulmonary tumor embolism involved not only the small peripheral arteries but also the segmental and/or lobar arteries.     

Reduced expression of tissue inhibitor of metalloproteinase (TIMP)-2 in gestational trophoblastic diseases

To elucidate the involvement of type IV collagenases [matrix metalloproteinase (MMP)-2 and MMP-9] and their tissue inhibitors (TIMP-1 and TIMP-2) in the development of gestational trophoblastic disease (GTD), we quantified their levels in hydatidiform mole and choriocarcinoma tissues using specific enzyme-linked immunosorbent assays, and the results were compared with those from normal first trimester placenta. Levels of pro-MMP-2 were increased in hydatidiform mole, and they were further elevated in choriocarcinoma. Levels of pro-MMP-9 in choriocarcinoma and those of TIMP-1 in both hydatidiform mole and choriocarcinoma were also increased. In contrast, TIMP-2 levels were markedly decreased in both hydatidiform mole and choriocarcinoma. Similar results were obtained by the tissue culture of first trimester placenta and hydatidiform mole. Gelatin zymography indicated that the levels of both pro- and activated forms of MMP-2 and MMP-9 were higher in hydatidiform mole and choriocarcinoma. The decreased expression of TIMP-2 in hydatidiform mole and choriocarcinoma was confirmed by Western blot, Northern blot and immunohistochemistry, with the decrease being more pronounced in choriocarcinoma. Taken together, the present study shows that both TIMP-2 mRNA and protein levels are markedly decreased in GTD and the imbalance of MMP-TIMP production, shifted toward greater MMP activity, may be involved in the pathogenesis of GTD.     

Insulin hypersensitivity in mice lacking the V1b vasopressin receptor

We have reported that [Arg⁸]-vasopressin-stimulated insulin release is blunted in islet cells isolated from V1b receptor-deficient ( V1bR ^−/−) mice. In this study, we used V1bR ^−/− mice to examine the physiological role of the V1b receptor in regulating blood glucose levels in vivo , and we found that the fasting plasma glucose, insulin and glucagon levels were lower in V1bR ^−/− mice than in wild-type ( V1bR ^+/+) mice. Next, we evaluated glucose tolerance by performing an intraperitoneal glucose tolerance test (GTT). The plasma glucose and insulin levels during the GTT were lower in V1bR ^−/− mice than in V1bR ^+/+ mice. An insulin tolerance test (ITT) revealed that, after insulin administration, plasma glucose levels were lower in V1bR ^−/− mice than in V1bR ^+/+ mice. In addition, a hyperinsulinaemic–euglycaemic clamp study showed that the glucose infusion rate was increased in V1bR ^−/− mice, indicating that insulin sensitivity was enhanced at the in vivo level in V1bR ^−/− mice. Furthermore, we found that the V1b receptor was expressed in white adipose tissue and that insulin-stimulated phosphorylation of Akt as an important signaling molecule was increased in adipocytes isolated from V1bR ^−/− mice. Thus, the blockade of the V1b receptor could result, at least in part, in enhanced insulin sensitivity by altering insulin signalling in adipocytes.     

In vitro controllability of the MagScrew total artificial heart system

The purpose of this study was to evaluate the in vitro responses to preload and afterload of our total artificial heart (TAH), the MagScrew TAH. The TAH consists of two blood pumps and a control logic, developed at the Cleveland Clinic, OH, and the MagScrew actuator and its electronic control system, developed by Foster-Miller Technologies, Inc., Albany, NY. Tests were performed on a mock circulatory loop, using water as a test fluid. Preload sensitivity of the Mag-Screw TAH demonstrated a Frank-Starling response to preload in automatic mode. A peak flow of 10 L/min was obtained, with a left atrial pressure of 13 mm Hg. The relationship between right atrial pressure and left atrial pressure was well balanced when tested with a left bronchial shunt flow of 5% and a range of pulmonary artery and aortic pressures. With respect to afterload response, the left pump showed a relatively low sensitivity, which allowed the pump to maintain perfusion over a wide range of aortic pressures. The right pump, on the other hand, was much more sensitive to pulmonary artery pressure, which provided a measure of protection against pulmonary congestion. The very effective physiologic response of the MagScrew TAH is believed to result from employment of a left master, alternating ejection control logic, high inherent sensitivity of the blood pumps to atrial pressure, a lower effective stroke volume for the right pump, and a scaling of right side motor ejection voltage to 80% of that used for the left side ejection.     

Adhesion activity of fetal gonadal cells to EGF and discoidin domains of milk fat globule-EGF factor 8 (MFG-E8), a secreted integrin-binding protein which is transiently expressed in mouse early gonadogenesis

MFG-E8, a secreted integrin-binding protein, consists of two EGF domains containing a RGD motif and two discoidin domains. In mouse embryogenesis, MFG-E8 is highly expressed in gonadal stromal cells near mesonephros at 11.5–12.5 dpc, but its function in gonadogenesis has not been characterized. To clarify a possible role of MFG-E8 in developing gonads, we analyzed the adhesion activity of 10.5–15.5 dpc gonadal cells to recombinant proteins of EGF or discoidin domains of MFG-E8. In EGF-coated wells, the gonadal cells at 11.5–12.5 dpc revealed a significantly higher adhesion activity as compared to those at 10.5 and 15.5 dpc, while discoidin domains showed a constant number of the adhered cells throughout these stages. To identify the adhesive cells of 11.5-dpc gonads, immunohistochemistry with anti-SF1/Ad4Bp antibody (a specific marker for supporting, steroidogenic, and coelomic epithelial cells) and staining for alkaline phosphatase (a germ cell marker) were carried out. As a result, EGF domains, as well as discoidin domains, were capable of binding to all three groups of SF1/Ad4Bp-positive and negative somatic cells, and germ cells of 11.5-dpc gonads. These findings therefore suggest that MFG-E8 mediates the cell-to-cell interaction among several somatic cell types and germ cells in mouse early gonadogenesis.