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Biomedical subjects

K Kawase

Publications and source records attributed to K Kawase.

At least 55 records · Page 3Linked to original sources

Low-dose and high-dose mitomycin trabeculectomy as an initial surgery in primary open-angle glaucoma.

PURPOSE: The purpose of the study is to determine the optimum regimen of intraoperative administration of mitomycin as an adjunct to trabeculectomy. METHODS: Of 11 patients with primary open-angle glaucoma, 22 eyes that had not undergone any surgical intervention were included. In each patient, one eye was randomly allocated to a mitomycin 0.2-mg group and the fellow eye to a mitomycin 0.02-mg group. Mitomycin was applied for 5 minutes only once during trabeculectomy. The follow-up period was 6 to 17 months. RESULTS: Eleven (100%) eyes in the 0.2-mg group and 7 (63.6%) in the 0.02-mg group achieved successful control of intraocular pressure with or without topical antiglaucoma medication. Transient hypotony maculopathy (18%) and cataract progression (18%) were noted in the 0.2-mg group exclusively. The incidence of other complications was similar between the two groups. CONCLUSION: These data suggest that the most appropriate dose of mitomycin for primary surgery seems to be in between the two doses tested in the current study.

Administration, Topical↗

Role of cell-binding in the antibacterial mechanism of lactoferricin B.

The antibacterial cell-binding properties of lactoferricin B, a potent bactericidal peptide derived from bovine lactoferrin, were investigated for the first time. To facilitate measurements of binding the peptide was radiolabelled by reduction and treatment with iodo-[1-14C]acetamide. 14C-lactoferricin B bound rapidly to the surface of Escherichia coli and Bacillus subtilis. The rate of binding was consistent with the rapid rate of killing caused by this peptide. The extent of binding was reduced in the presence of Mg2+ or Ca2+ ions which act to reduce its antimicrobial effectiveness. The optimal pH for binding was strain-dependent and the killing effect was maximal near the optimal pH for cell binding with each strain tested. These observations indicate that direct interaction of lactoferricin B with the cell surface is necessary for its lethal effect. The number of peptide molecules bound (> 10(6) per cell) was more than would be expected for binding to specific protein receptors. Lactoferricin B inhibited bacterial uptake of 3H-proline with effectiveness similar to polymyxin B, a known membrane-disruptive agent. The cell-binding event appears to lead to a disruption of normal permeability functions of the cytoplasmic membrane.

Anti-Bacterial Agents↗

[Surgical stress induces the secretion of alpha human atrial natriuretic peptide].

The changes in plasma alpha-hANP level and the factors affecting its secretion were studied in 35 patients treated by surgery for gastrointestinal disease (laparotomy group, 17) and (non-laparotomy group, 18). They did not have any particular complication during the study period. alpha-hANP, catecholamine (CA), antidiuretic hormone (ADH), aldosterone and plasma renin activity (PRA) were determined serially before and after the surgery. Plasma alpha-hANP level elevated on the post-operative day 1 and dropped to the upper limit of the normal range by the day 3, then gradually recovered to the level of before surgery. This early elevation of alpha-hANP was more marked in the laparotomy group than in the non-laparotomy group. These change in alpha-hANP level correlated well to those of CA, but not to those of ADH, aldosterone, and PRA. Age, sex, duration of surgery, bleeding and infusion volume during surgery did not affect the difference in alpha-hANP secretion between the two groups. In conclusion, the early elevation of plasma alpha-hANP level was correlated well to the surgical stress, and that this alpha-hANP secretion might be induced by CA secretion.

Adult↗

Anterior chamber reaction after mitomycin and 5-fluorouracil trabeculectomy: a comparative study.

We measured aqueous flare in 16 glaucomatous eyes after trabeculectomy in which 5-fluorouracil (5-FU) or mitomycin C (MMC) had been used as an adjunctive therapy. The eyes were divided into a 5-FU and an MMC group, matched for factors that might influence the postoperative inflammatory response to intraocular surgery. Seven eyes of seven patients received subconjunctival injections of 5-FU (50 mg in 2 weeks) and nine eyes of nine patients were given 0.2 mg/0.5 mL MMC intraoperatively. The aqueous flare converted to an albumin concentration (mg/dL) was significantly higher in the 5-FU group than in the MMC group (359.6 +/- 113.8 mg/dL and 143.2 +/- 46.7 mg/dL, respectively; Mann-Whitney U test, P < .05) on the second postoperative day. Intraoperative MMC appears to be no more harmful to the blood-aqueous barrier than 5-FU.

Anterior Chamber↗

[Treatment of advanced gastric and colorectal cancer with 5-FU, leucovorin and interferon-alpha].

Twenty-four patients with advanced or relapsed gastric or colorectal cancer were treated with a combination of 5-fluorouracil (5-FU), leucovorin (LV) and interferon-alpha (IFN-alpha). 5-FU was administered by rapid intravenous infusion at 350 mg/m2 for 5 consecutive days. Intravenous bolus administration of LV 20 mg/m2 was given before each 5-FU administration. This combination was repeated every 3 to 4 weeks. IFN-alpha (HLBI), 6MU, was administered subcutaneously daily. Of 13 patients with gastric cancer, there were 2 PR, 4 NC and 7 PD, and among 11 patients with colorectal cancer, there were 1 CR, 8 NC and 2 PD. All 16 previously treated patients had no clinical response. Responses were seen in patients with no prior chemotherapy and with good performance status. Most common toxicities observed were leucopenia, fever, stomatitis and diarrhea, which were all tolerable and reversible.

Adult↗

Identification of the bactericidal domain of lactoferrin.

We report the existence of a previously unknown antimicrobial domain near the N-terminus of lactoferrin in a region distinct from its iron-binding sites. A single active peptide representing this domain was isolated following gastric pepsin cleavage of human lactoferrin, and bovine lactoferrin, and sequenced by automated Edman degradation. The antimicrobial sequence was found to consist mainly of a loop of 18 amino acid residues formed by a disulfide bond between cysteine residues 20 and 37 of human lactoferrin, or 19 and 36 of bovine lactoferrin. Synthetic analogs of this region similarly exhibited potent antibacterial properties. The active peptide of bovine lactoferrin was more potent than that of human lactoferrin having effectiveness against various Gram-negative and Gram-positive bacteria at concentrations between 0.3 microM and 3.0 microM, depending on the target strain. The effect of the isolated domain was lethal causing a rapid loss of colony-forming capability. Our studies suggest this domain is the structural region responsible for the bacterial properties of lactoferrin.

Amino Acid Sequence↗

Mitomycin concentration in rabbit and human ocular tissues after topical administration.

The authors measured mitomycin C (MMC) concentrations in ocular tissues with high-performance liquid chromatography. Mitomycin C concentration after a single subconjunctival injection of the drug in rabbit eyes showed a rapid decrease with a half-life of 0.18 to 0.30 hours for the conjunctiva and 0.20 to 0.45 hours for the sclera at the injection site. Irrigating the ocular surface with 200 ml of saline after MMC application reduced the initial drug concentration to one fifth in the sclera and to one fifteenth in the conjunctiva but did not change the half-life. The MMC concentration in human trabeculectomy specimens obtained immediately after MMC application (0.2 mg/0.5 ml) and irrigation was 5.4 to 12.0 micrograms/g with a mean of 8.4 micrograms/g, a level similar to that in the rabbit sclera immediately after the irrigation after administration of the same MMC dose. These results indicate that MMC disappears rapidly from the ocular tissues and that irrigating the tissues significantly reduces the tissue concentration of MMC.

Administration, Topical↗

Composition and turnover of phospholipids and neutral lipids in human breast cancer and reference tissues.

The phospholipid (PL) content was 4-fold higher while the triacylglycerol (TG) content tended to be 65% lower in human breast cancer tissues as compared with non-cancerous reference parts from excised breast tissues. The variation in TG content among breast tissues was very large while that of PL was relatively small. The fatty acid compositions of PL were significantly different between the cancer and reference tissues; the proportions of octadecenoate (18:1), docosahexaenoate (22:6n-3), the total n-3 fatty acids and the n-3/n-6 ratio, but not the proportion of arachidonate (20:4n-6), were significantly higher in the major PL of cancer tissues as compared with those of the reference tissues. No significant differences were observed in the proportion of the major fatty acids of TG in these tissues. The turnover of lipids was faster in the cancer tissues than in the reference tissues. The turnover of TG was faster than that of PL in the cancer tissues, whereas the opposite was true in the reference tissues, indicating significant differences in lipid metabolism between these tissues. A striking difference in the n-3 and n-6 fatty acids of the reference tissues noted for Japanese and Finnish women is discussed in relation to the roles of eicosanoids and eicosanoid precursors in mammary carcinogenesis.

Adult↗

Maternal transmission of HTLV-1 other than through breast milk: discrepancy between the polymerase chain reaction positivity of cord blood samples for HTLV-1 and the subsequent seropositivity of individuals.

We used a nested polymerase chain reaction (PCR) to diagnose HTLV-1 carriers. The DNA isolated from the nuclear extract obtained from frozen whole blood was found appropriate for PCR study both qualitatively and quantitatively. The use of freshly frozen whole blood made the field work much easier, and the use of a nuclear extraction procedure allowed DNA isolation in just 4 microcentrifuge tubes. We could not attain sufficient sensitivity to detect a single molecule with single-step PCR, but nested PCR was confirmed to detect a single molecule/reaction. All samples of the seropositive group including 94 blood donors, 66 mothers, and 13 children were positive in the nested PCR, while none of the seronegative group, including 198 blood donors and 285 children, was positive. Although 18/717 (2.5%) cord blood samples obtained from babies born to carrier mothers were PCR-positive, none of 5 formula-fed children tested who had been PCR-positive in the cord blood gave evidence of infection later on. Furthermore, all of 4 seropositive infected children who were formula-fed had been PCR-negative in their cord blood. The results are not consistent with intrauterine infection, but suggest the presence of a perinatal or postnatal infection route other than through breast milk.

Base Sequence↗

Antibacterial spectrum of lactoferricin B, a potent bactericidal peptide derived from the N-terminal region of bovine lactoferrin.

A physiologically diverse range of Gram-positive and Gram-negative bacteria was found to be susceptible to inhibition and inactivation by lactoferricin B, a peptide produced by gastric pepsin digestion of bovine lactoferrin. The list of susceptible organisms includes Escherichia coli, Salmonella enteritidis, Klebsiella pneumoniae, Proteus vulgaris, Yersinia enterocolitica, Pseudomonas aeruginosa, Campylobacter jejuni, Staphylococcus aureus, Streptococcus mutans, Corynebacterium diphtheriae, Listeria monocytogenes and Clostridium perfringens. Concentrations of lactoferricin B required to cause complete inhibition of growth varied within the range of 0.3 to 150 micrograms/ml, depending on the strain and the culture medium used. The peptide showed activity against E. coli O111 over the range of pH 5.5 to 7.5 and was most effective under slightly alkaline conditions. Its antibacterial effectiveness was reduced in the presence of Na+, K+, Mg2+ or Ca2+ ions, or in the presence of various buffer salts. Lactoferricin B was lethal, causing a rapid loss of colony-forming capability in most of the species tested. Pseudomonas fluorescens, Enterococcus faecalis and Bifidobacterium bifidum strains were highly resistant to this peptide.

Amino Acid Sequence↗

Trabeculectomy with mitomycin. A comparative study with fluorouracil.

We conducted a prospective, randomized study to compare mitomycin with fluorouracil for efficacy and safety as an adjunct to trabeculectomy in eyes with glaucoma with poor surgical prognosis. Thirty-two eyes of 32 patients were randomly allocated to either mitomycin (17 eyes) or fluorouracil therapy (15 eyes). Mitomycin (0.2 mg) was applied only once during trabeculectomy, and fluorouracil (5 mg) was subconjunctivally injected 10 times in the 2 weeks after surgery. Fifteen eyes (88%) in the mitomycin group and seven (47%) in the fluorouracil group achieved an intraocular pressure of less than or equal to 20 mm Hg without antiglaucoma medication. The follow-up period was 7 to 12 months. Corneal complications were less common in the group given mitomycin than in that given fluorouracil (12% vs 53%). The incidence of other complications was similar between the two groups.

Adult↗

Potent antibacterial peptides generated by pepsin digestion of bovine lactoferrin.

The antibacterial properties of enzymatic hydrolysates of bovine lactoferrin were examined to determine whether active peptides are produced from this protein. Hydrolysates prepared by cleavage of lactoferrin with porcine pepsin, cod pepsin, or acid protease from Penicillium duponti showed strong activity against Escherichia coli O111, whereas hydrolysates produced by trypsin, papain, or other neutral proteases were much less active. Low molecular weight peptides generated by porcine pepsin cleavage of lactoferrin showed broad-spectrum antibacterial activity, inhibiting the growth of a number of Gram-negative and Gram-positive species, including strains that were resistant to native lactoferrin. The antibacterial potency of the hydrolysate was at least eightfold greater than that of undigested lactoferrin with all strains tested. The active peptides retained their activity in the presence of added iron, unlike native lactoferrin. The effect of the hydrolysate was bactericidal as indicated by a rapid loss of viability of E. coli O111. The lactoferrin hydrolysate described in the present study has commercial value as a natural preservative agent for use in foods and cosmetics, and as a functional component of new clinical foods for prevention or treatment of gastrointestinal disease.

Animals↗

A case of small bowel carcinoma in Crohn's disease.

A 46-year-old man had symptoms of ileus four years and five months after being diagnosed as Crohn's disease. Upon small bowel radiography, a short, spindle shaped stenosis on the distal site of the ileum was found. In the resected specimen, there was a constricted area with wall hypertrophy, and the mucosal surface of this region was rough and granular. At the site of this region, well differentiated adenocarcinoma was noted, which infiltrated the serosa in the form of mucous adenocarcinoma. Transmural disproportional inflammation and non-caseating granuloma were also around there. The X-ray findings in this case are considered to be useful for diagnosis of carcinoma during the long term observation period for Crohn's disease.

Adenocarcinoma↗

Amplification of HTLV-1-related sequences among patients with neurological disorders in highly endemic Nagasaki: lack of evidence for association of HTLV-1 with multiple sclerosis.

We studied DNA sequences homologous to HTLV-1 in peripheral blood mononuclear cells (PBMC) of 30 patients with neurological disorders in Kyushu, where HTLV-1 is highly endemic. The regions of HTLV-1 amplified by means of polymerase chain reaction (PCR) included U3, U5, gag, pol, env and pX. Our system specifically detected HTLV-1 sequences only from HTLV-1-positive cells and was sufficiently sensitive to detect one proviral copy per 10(3) PBMC. All PCR-positive cases were seropositive, including 4 cases of tropical spastic paraparesis/HTLV-1-associated myelopathy (TSP/HAM) (4/4), and one case each of myasthenia gravis (1/7) and multiple sclerosis (1/8). The PCR-positive rate of patients, excluding 4 TSP/HAM cases, was 8% (2/26), which is similar to the seroprevalence of the adult population in the area. The data suggest that multiple sclerosis is not associated with prototype HTLV-1.

Adult↗

[Electrocardiogram in pulmonary heart disease--clinical evaluation of right chest leads].

A clinical study was made to evaluate the usefulness of electrocardiograms in right precordial leads (V3r or V4R) for the diagnosis of cardiac complications among patients with chronic pulmonary disease. Walsh and colleagues reported that the change of direction in the terminal vector of QRS loop in the vector cardiogram is useful for the evaluation of chronic pulmonary heart disease. They showed that the terminal vectors of QRS loops tend to deviate to the right and/or posterior direction in the early stage of chronic pulmonary heart disease. We utilized the electrocardiograms in the right precordial leads to detect the second R waves, which are thought to reflect the terminal vectors of QRS loops in the vectorcardiograms. When the electrocardiograms in the right precordial leads were compared, the second R waves in leads V3R or V4R were more frequently observed among patients with chronic pulmonary heart disease than those without. However, in the same two groups, the frequency of second R waves in leads V5R or V6R didn't differ. We conclude that the second R waves in leads V3R or V4R in a patient with chronic lung disease suggest the presence of chronic pulmonary heart disease as a complication.

Adult↗

[A case of secretory carcinoma of the breast in a elderly Japanese woman].

We report a case of a secretory carcinoma of the breast in a 72-year-old woman with a long history of a left breast mass. Rapid growth and skin invasion of the tumor was noticed three months before a radical mastectomy was performed and a lung metastasis was found one month after the operation. A metastasis to the axillary nodes was noted in 6 of 9 resected specimens and a receptor assay of the estrogen and progesterone proved to be negative. This patient is the oldest case of a secretory carcinoma of the breast reported in Japan.

Adenocarcinoma↗