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Biomedical subjects

Y Hiki

Publications and source records attributed to Y Hiki.

At least 55 records · Page 3Linked to original sources

Reactivity of glomerular and serum IgA1 to jacalin in IgA nephropathy.

To analyze O-linked oligosaccharides (O-glycans) in the hinge region of IgA1 in IgA nephropathy (IgAN), the reactivity of IgA1 to jacalin, which specifically binds to O-glycans, was investigated. Initially, renal biopsy specimens from 5 patients with IgAN and 3 patients with other renal diseases were investigated in an immunofluorescence study with jacalin, monoclonal antihuman IgA1 and IgA2 antibodies. All of the renal biopsy specimens of IgAN and none of other renal diseases were positively stained by both FITC-labeled jacalin and monoclonal anti-IgA1 antibody. The glomerular staining patterns of FITC-jacalin were similar to those of the monoclonal anti-IgA1 antibody. IgA2 was negative in all specimens. Based on the positive reactivity of deposited IgA1 to jacalin, the binding ability of serum IgA1 to jacalin was evaluated by inhibition assay using D-galactose in patients with IgAN (n = 58), other primary glomerulonephritides (PGN) (n = 41), and healthy controls (n = 52). The frequencies of the patients with serum IgA1 having a high affinity for jacalin were significantly greater in IgAN (19/58, 32.8%) compared with the healthy controls (2/52, 3.8%) and other PGN (4/41, 9.8%). These results suggested that the increased reactivity of O-glycan(s) in the IgA1 hinge region to jacalin is due to an unusual glycosylation of serum IgA1 in IgAN.

Adult↗

Association of asialo-galactosyl beta 1-3N-acetylgalactosamine on the hinge with a conformational instability of Jacalin-reactive immunoglobulin A1 in immunoglobulin A nephropathy.

The O-glycans in Jacalin-binding immunoglobulin A1 (IgA1) were released by gas-phase hydrazinolysis and were fractionated by gel filtration and reversed-phase HPLC. Four peaks (P1 to P4) were obtained. There was a significant shift from Peak 2 (monosialylated Gal beta 1-3GalNAc) to Peak 4 (asialo-Gal beta 1-3GalNAc) in the IgA-nephropathy group compared with the negative control group (P < 0.05). One of the functions of the carbohydrate side chains is to stabilize the three-dimensional structure of the glycopeptides. In order to evaluate the stability of the Jacalin-binding IgA1 molecule, the increase in turbidity as a consequence of the increase of the aggregated IgA1 level under the condition of high temperature (63 degrees C) was observed. The increase in the turbidity was significantly higher in the IgA nephropathy group compared with the negative control group (21.7 vs. 5.9% at 150 min, P < 0.02). From a sample of IgA1 solution that had originated from a pooled normal serum, heat-tolerant (nonaggregated) and intolerant (aggregated) IgA1 molecules were separated by gel filtration. The heat-intolerant IgA1 had lower amounts of sialic acid (27.4 micrograms/mg IgA1) than the tolerant IgA1 (37.6 micrograms/mg IgA1). Further, the analysis of the O-glycans released from another IgA1 sample by the hydrazinolysis revealed that the ratio of the asialo-Gal beta 1-3GalNAc/total Gal beta 1-3GalNAc in the heat-in-tolerant IgA1 (27.2%) was increased compared with that in the heat-tolerant IgA1 (18.2%). From these results, it was suggested that unusual glycosylation on the hinge region of Jacalin-binding IgA1 induced an insufficient conformational stiffness to the hinge peptide, resulting in the aggregation of the IgA1 molecule in IgA nephropathy.

Acetylgalactosamine↗

[Photodynamic therapy for esophageal cancer].

Evaluation of resected cases of esophageal superficial cancer have shown that lymph node metastasis was absent, and radical local treatment would be possible for m1 and m2 cancer. However, the depth of cancer invasion is difficult to diagnose before treatment. Endoscopic mucosal resection (EMR) is useful for not only treating but also diagnosing cancer. Therefore, EMR is recommended as the treatment of choice for m1 or m2 lesions. On the other hand, treatment of esophageal superficial cancer by PDT is effective even for deep sm cancers. In particular, the use of excimer dye laser increases light transmittance, there by improving the treatment results for sm cancer. EMR was not effective for treating sm cancer or diagnosing the depth of its invasion. In sm cancer, since lymph node metastasis is observed in 30-50% of the cases, local treatment cannot be radical. Therefore, PDT is best indicated as a local treatment for sm cancer that cannot be treated by operation. Local healing after PDT prevents dysphagia caused by stenosis due to cancer, which may allow medical management at home.

Antineoplastic Agents↗

[Endoscopic mucosal resection (EMR) for early gastric cancer].

The treatment of early gastric cancer using an endoscopy, namely, endoscopic mucosal resection (EMR), has been employed in the world, especially in Japan from the beginning of 1980s. It has the advantage of enabling histopathological exploration of the resected specimen. This study involved of patients with solitary early gastric cancer who underwent a radical operation at the department of surgery, School of Medicine, Kitasato University. They selected from a retrospective study of the presence of lymph node metastasis based on histopathological findings. It was found that the early gastric cancer with negative lymph node appeared as an elevated tumor with the diameter of 2.5 cm or less; or concave tumor with the diameter of 2.0 cm or less and without concomitant ulcer in the lesion. Moreover, histologically differentiated adenocarcinoma and the invasion depth of m were desirable conditions for EMR. The above mentioned conditions were defined as the indications for EMR in a broad sense. This study redefined the size of a tumor that could be completely removed by one EMR. It has become clear that, based on our experience, the conditions should be strictly revised as follows; elevated tumors with the diameter of 2.0 cm or less and concave tumors with the diameter of 1.0 cm or less (absolute indications). If EMR is first selected for early gastric cancers under these strict conditions, it would promise the same favorable long-term survival rate as we experienced.

Endoscopy↗

[Binding of IgA1 to monocyte/macrophage cell lines (THP-1, U937) in IgA nephropathy--a possible role of O-glycan in the IgA1 molecule].

IgA1 is an exceptional serum glycoprotein because it has O-glycans in the hinge region. It has been observed that the monocyte/macrophages infiltrate within the glomeruli in IgA-N. On the other hand, it is well established that the carbohydrate side chains (N-glycans) of the IgG molecule play a role in the binding of IgG to Fc receptors. Therefore, the binding of IgA1 to monocyte/macrophage cell lines was observed with the aim of clarifying the role of the O-glycan side chains in IgA-N in the initial mechanism of glomerular damage due to the interaction between the O-glycan chains on the IgA1 molecule and infiltrating monocyte/macrophages. Two human myelomonocytic cell lines, THP-1 and U-937, were activated and incubated with separated IgA1 (IgA-N, n = 16; other glomerulonephritides (other GN), n = 15; healthy controls, n = 9). The binding attitude of IgA1 to the cell lines was observed by flow immunofluorometry using a FACScan. FACScan showed that the binding of IgA1 to both of the stimulated monocyte/macrophage cell lines was increased in IgA-N compared to the normal controls and other GN. The binding of IgA1 to THP-1 was partially, but definitely inhibited by adding 100 mM melibiose (19.6 +/- 7.7%) and galactose (13.1 +/- 2.9%), but not glucose (2.9 +/- 2.2%), lactose (4.7 +/- 4.7%) and mannose (3.3 +/- 3.3%). These results suggested that THP-1 had a receptor that recognized the O-glycan in the IgA1 hinge region.(ABSTRACT TRUNCATED AT 250 WORDS)

Cell Line↗

[Experience and problems with home parenteral nutrition for patients with peritonitis carcinomatosa].

Since 1987, we have been using home parenteral nutrition (HPN) for patients with peritonitis carcinomatosa, who had undergone surgery for cancer of the digestive tract and who could not take food orally. We have been inserted catheterization for HPN in 90 patients. Nine of them underwent the treatment as training, but HPN was possible in the remaining 81 patients (90%). The patients in whom the treatment failed to be transferred to HPN showed worsening of their general condition during hospitalization, because the period of training was long. As a result, they could not be discharge. We considered that the timing of transfer to HPN was inappropriate. The largest number of patients, 57, had undergone surgery for cancer of the stomach and esophagus, which was the underlying disease. The mean period of HPN was 108.2 days. According to the underlying disease, the period was longest, 115.7 days, for cancer of the stomach and esophagus, followed by 93.8 days for colorectal cancer. The performed rate of HPN for 60, 90, 180 and 270 days were 56.7, 36.0, 17.9 and 6.5%, respectively, with the one-year cumulative rate of 3.3%. HPN for terminal stage of cancer is an effective treatment for patients with peritonitis carcinomatosa, and it allowed improvement in the quality of life. Cooperation with various medical staff members is also necessary and a hospital system should be established for safe and smooth achievement of the treatment method.

Ascitic Fluid↗

[Effect of prophylactic intra-arterial infusion of anticancer drugs on post hepatic resection for hepatic metastasis of colorectal cancer].

Prophylactic intra-arterial infusion of anticancer drug on post hepatic resection for hepatic metastasis of colorectal carcinoma were performed 8 cases. In our cases consisted of 8 patients of mean age of 54.3 years (male 3 cases and female 5 cases, synchronous metastasis 4 cases and metachronous 4 cases). All patients were received intra-arterial bolus injection of MMC (4-8 mg/body) at day 1 and continuous infusion of 5-FU (250-750 mg/body) for 7 days on admission. After discharged, patients were received bolus injection of 5-FU (250-750 mg/body) for once a week. Side effect of this treatment was not appeared and all of them obtained very good QOL. There were no recurrence sign of residual liver and this procedure was very useful method for post hepatic resection for hepatic metastasis of colorectal cancer.

Adult↗

A case of Recklinghausen neurofibromatosis associated with membranous nephropathy.

A 68-year-old woman who had a history of Recklinghausen neurofibromatosis from 1964 showed nephrotic syndrome in 1989. Renal biopsy revealed membranous nephropathy. Various suspected causes of secondary membranous nephropathy were not found. Coexistence of Recklinghausen neurofibromatosis and membranous nephropathy has rarely been reported.

Aged↗

Intragastric pH in postlaparotomy patients--effects of cimetidine.

Intragastric pH was continuously monitored in 21 patients who underwent colorectal surgery. Monitoring was started before surgery, and was continued for two days after surgery. Intragastric pH tended to increase during surgery, compared with measurements obtained before and after surgery, but was not affected by the duration of anesthesia or of the surgical procedure, or surgical position. After surgery, patients were divided into two groups: the cimetidine group (10 patients) received intravenous cimetidine 200 mg 4 times a day, while the control group (11 patients) received no treatment. Postoperative intragastric pH was higher than 3.0 throughout the study in the cimetidine group, but was approximately 1.3 in the control group. Upper gastrointestinal bleeding occurred in 2 patients in the control group, with intragastric pH falling abruptly during the bleeding episode. To prevent post-operative upper gastrointestinal bleeding, in addition to the administration of H2-blockers or antacids, appropriate treatments in response to changes in intragastric pH are necessary. Continuous monitoring of intragastric pH in surgical patients is considered to be of clinical importance.

Aged↗

[Prognostic significance of persistent massive proteinuria in progressive IgA nephropathy--a long-term follow-up study].

The most reliable factors predicting a long-term prognosis in individual progressive IgA nephropathy patients were evaluated. Ninety-eight cases who showed moderate to severe histological alterations (total score of 7 or more) and were continuously followed up for 10 years or more from the first biopsy were the subjects of this study. During the follow-up period of 10 years, 52 of the 98 cases went into hemodialysis treatment (HD). All 24 cases who had a higher total score of 17 or more, or severe renal dysfunction of less than 60 ml/min in their initial Ccr values went into HD. The remaining 74 cases who showed both a total score below 16 and initial Ccr values of 60 ml/min or more were divided into two groups in their clinical courses: 28 (group I) of the 74 cases went into HD and the other 46 (group II) did not. The degree of initial proteinuria was significantly different between groups I and II, but the degree of individual proteinuria was in a similar range from 0.5 to 2.5 g/day in most cases of both groups. Therefore, in order to clarify a more precise factor associated with the individual prognosis, the % duration of massive proteinuria (% DP) was calculated in individual cases. The % DP was more significantly different between groups I and II (82.6 +/- 26.1 vs 19.6 +/- 27.3%, p < 0.01). Moreover, all cases but one in group I showed 30% or more in % DP and 35 of 46 cases in group II showed 30% or less.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

The significance of tubulointerstitial nephritis in IgA nephritis.

The occurrence of significant tubulointerstitial nephritis (TIN) was observed in 6 (18.3%) of 32 patients with IgA nephritis registered in 1991. T lymphocytes and macrophages in the interstitium were seen to invade the tubulus through injured tubular basement membrane (TBM), then were seen in the intercellular spaces of tubular cells which showed degeneration, single cell necrosis or detachment. Thus some tubular components were seen destroyed and had disappeared resulting in interstitial fibrosis, and others showed a regeneration process forming a renewed TBM on the innerside of the original TBM. However the recurrence of cellular inflammation was again observed in these regenerated tubuli. Thus the progression of nephron loss by TIN was seen to be independent of the glomerular changes and TIN is considered to be one of the important factors in predicting the prognosis of IgA nephritis.

Adolescent↗

[Early phase II study of FUT-187 (sepimostat mesilate) on reflux esophagitis--mainly on postgastrectomy reflux esophagitis].

An early phase II clinical study with the proteolysis inhibitor FUT-187 was carried out on patients with reflux esophagitis. FUT-187 was administered orally at the dose of 300 mg/day or 400 mg/day four times daily, after meals and at bedtime, for 4 consecutive weeks. The total number of patients admitted to this study was 40, of whom 9 were assigned to 300 mg/day group and 31 to 400 mg/day group. The rate of effectiveness on postgastrectomy reflux esophagitis was 88% (7/8) in 300 mg/day group and 85%(22/26) in 400 mg/day group when "improved" or better final general improvement ratings were taken into consideration, and 75% (6/8) in 300 mg/day group and 69% (9/13) in 400 mg/day group when "improved" or better endoscopic general improvement ratings were used. The overall safety rating "no problem as to the drug safety" was 89% (8/9) in 300 mg/day group and 71% (22/31) in 400 mg/day group. The main side effect was diarrhea, which was experienced in 6 patients in 400 mg/day group. However, it was resolved by discontinuation of the drug treatment. Other symptoms of gastrointestinal upsets, such as nausea and anorexia, were also induced. Based on these results, it may be concluded that FUT-187 can be a drug with clinical utility that benefits postgastrectomy reflux esophagitis at the dose level of 300 mg/day or less.

Administration, Oral↗

Photodynamic therapy for cancers: a clinical trial of porfimer sodium in Japan.

Photodynamic therapy utilizing Photofrin has proven to be an effective modality that can be used in the treatment of a wide variety of solid tumors and luminal cancers. An argon pumped dye laser or excimer dye laser was used to deliver 630 nm light via quartz fibers passed through the biopsy channel subsequent to i.v. injection of photosensitizer. In this study, 64 patients with superficial cancers were treated in this manner but only 58 patients, including 21 with roentgenographically occult lung cancer, 8 with stage I lung cancer, 5 with esophageal cancer, 12 with gastric cancer, 8 with cervical cancer and 4 with bladder cancer were evaluable. Complete remission was obtained in 48 out of 58 cases (82.8%). There was no serious complication except skin photosensitivity, which was seen in 13 patients. We conclude that photodynamic therapy is efficacious in the treatment of superficial cancers where complete remission may be achieved.

Adult↗

A case of severe IgA nephropathy associated with psoriatic arthritis and idiopathic interstitial pneumonia.

A patient is described with severe IgA nephropathy associated with psoriatic arthritis, idiopathic interstitial pneumonia and brain hemorrhage that developed serially over one and a half years. The histological findings of the renal biopsy showed severe endo- and extracapillary proliferative glomerulonephritis. Massive IgA deposits were observed by immunofluorescence not only in the mesangium but also along the capillary walls. Electron microscopy revealed abundant electron-dense deposits in the mesangial and subendothelial areas. The overlapping or coexistence of these conditions has rarely been reported.

Adult↗