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Biomedical subjects

F Ito

Publications and source records attributed to F Ito.

At least 19 recordsLinked to original sources

Surgical Management of Young Women with High-Risk Breast Cancer Receiving Neoadjuvant Systemic Therapy on the I-SPY2 Trial.

BACKGROUND: Mastectomy rates in women with breast cancer are higher in younger women than in older women. The impact of this more extensive surgery on overall survival (OS) and locoregional recurrence in younger women is unknown, especially after neoadjuvant systemic therapy (NST). This study evaluated surgical management and outcomes of patients aged &#x2264; 45 versus > 45 years enrolled in multicenter NST clinical trial, I-SPY2.0 (NCT01042379, PMID 37325931). METHODS: We conducted a secondary data analysis comparing locoregional treatment in patients aged &#x2264; 45 versus > 45 years with clinical or molecular high-risk clinical stage II-III breast cancer treated from April 2010 to June 2022. Multivariate Cox proportional hazards models were used to evaluate associations between type of breast surgery with OS and locoregional recurrence-free interval by age group and tumor receptor subtype. RESULTS: Of 1737 patients, 698 (40.2%) were aged &#x2264; 45 years. There were no significant differences in patient or tumor characteristics or residual cancer burden distribution between age groups. Although breast-conserving surgery was significantly less common in younger women (36.8% vs 48.5%, p < 0.001), surgery type was not associated with OS or locoregional recurrence-free interval for patients aged &#x2264; 45 years. CONCLUSIONS: Greater extent of breast surgery was not associated with improved outcomes in women aged &#x2264; 45 years. Choice of surgical procedure in the management of breast cancer is multifactorial, but young age alone&#xa0;does not warrant mastectomy following NST.

Breast cancer

Serum bilirubin fractions in cholestatic pediatric patients: determination with Micronex high-performance liquid chromatography.

Bilirubin conjugates in the serum of cholestatic pediatric patients were investigated with Micronex high-performance liquid chromatography. Serum bilirubin was resolved into four fractions: delta bilirubin (Bd), bilirubin diglucuronide (BDG), bilirubin monoglucuronide (BMG), and unconjugated bilirubin (Bu). The conjugated bilirubin (BDG+BMG) fraction in preoperative patients with biliary atresia (BA) was 48.8 +/- 5.1%, which was significantly higher than that in patients with infantile hepatitis (P < .01). Among postoperative BA patients who recovered from jaundice, the Bd fraction increased during the first month, remained elevated (60% to 80%) for a while, and then gradually decreased. After 6 months, the Bd fraction decreased to 30% in the jaundice-free survivors, but was still higher than that in controls (7%). Even after the total serum bilirubin had normalized (< or = 1.0 mg/dL), distribution of bilirubin fractions remained abnormal, possibly reflecting impaired hepatic excretion of bilirubin. In conclusion, measurement of the conjugated bilirubin fraction enabled BA to be differentiated from infantile hepatitis, and the delta bilirubin fraction proved to be an important indicator of cholestasis in postoperative BA patients with normal serum bilirubin.

Biliary Atresia

A case of massive adrenal malignant pheochromocytoma: management of a large pheochromocytoma.

A 69-year-old man was referred to our hospital for a left abdominal tumor measuring about 30 cm in diameter. Laboratory examination revealed an elevation of norepinephrine in plasma and of its metabolites in urine. CT scan disclosed a huge cystic tumor in the retroperitoneal space and an enlarged aortocaval lymph node, suggesting a diagnosis of malignant pheochromocytoma. The hemodynamic studies showed low blood volume and high vascular resistance, and therefore, he was treated with vasodilators and volume expansion. His hemodynamic status normalized and a complete excision was performed. Pathological examination revealed that the patient had a pheochromocytoma with metastasis to a lymph node. The total weight of the tumor was 5,930 g. Since pheochromocytomas can become a large with a risk of malignancy, they should be surgically excised as completely as possible with further treatment after making a definite diagnosis.

Adrenal Gland Neoplasms

Comparison of sperm preparation methods. Wash and concentration, swim-up, migration-gravity sedimentation, 80% Percoll and semen filtration column.

The removal of all debris and background, as well as antifertility factors present in seminal fluid, may increase the fertilizing ability of spermatozoa. A number of semen manipulative techniques are currently available to remove the undesirable spermatozoa, debris and other factors and to increase sperm quality before performance of the various assisted reproductive technologies. We compared the impact of the wash and concentration method, swim-up method, 80% Percoll method, migration-gravity sedimentation method and SpermPrep method on postmanipulation sperm quality.

Adult

[A clinico-pathological study of renal cell carcinoma with a diameter of less than 5 cm].

To examine the indication of nephron sparing operations, we searched 31 nephrectomized kidneys with renal cell carcinoma for small associated lesions in the normal-appearing portion of these kidneys. The diameter of the predominant tumors was between 15 and 50 mm. The kidneys were serially sectioned at 5-mm intervals, and all sections were examined microscopically. Two of the 31 kidneys had a small renal cell carcinoma, and four had a small adenoma in the normal-appearing portion. We recommend that the nephron-sparing operation should be is performed limitedly and that radical nephrectomy is yet a standard operation in the presence of a normal contralateral kidney.

Adenoma

Feasibility of agarose microbeads with xenogeneic islets as a bioartificial pancreas.

A bioartificial pancreas, that is, transplantation of islets of Langerhans (islets) which are enclosed in a semipermeable membrane, has been proposed as a treatment for type I diabetes. The islets are immuno-isolated from the host by the semipermeable membrane preventing rejection while maintaining control of glucose metabolism for an extended period. The purpose of the current research is to evaluate the feasibility of preparing agarose microbeads with xenogeneic hamster islets as a bioartificial pancreas in streptozotocin induced diabetic mice. In the recipients with a low level of anti-hamster antibodies, the combination of encapsulation of hamster islets in 5% agarose microbeads and in vitro culture of them prolonged xenograft survivals. Four of 6 recipients were still normoglycemic at 100 days after implantation. However, the same procedure was not effective in the recipients which were sensitized in advance by transplantation of free hamster islets and thus had high levels of anti-hamster antibodies. The average normoglycemic period was 32 days. Antibodies permeated through the microbeads and activated complement on the cell surfaces. The network of agarose microbeads was rendered dense by increasing the concentration of agarose to restrict the diffusion of antibodies. Graft survivals were prolonged with increasing concentrations of agarose. As an analysis using diffusion equations predicted, the survivals were inversely proportional to the diffusion coefficient of IgG in each agarose gel. Islet xenotransplantation was enabled by the combination of the microbeads with a concentration of agarose higher than 7.5% and in vitro culture even in recipients having a high level of preformed antibodies.

Animals

Basic fibroblast growth factor (FGF-2) in renal cell carcinoma, which is indistinguishable from that in normal kidney, is involved in renal cell carcinoma growth.

To investigate the role of basic fibroblast growth factor (FGF) in renal cell carcinoma growth, we have analyzed the expression of mRNA of basic FGF. In 7 of 15 cases, basic FGF mRNA level in renal cell carcinoma tissues was higher than that in corresponding normal tissues. However, the tumor-to-normal ratios of expression levels are chiefly less than 2.0 and, in 5 cases, are even less than 1.0. Furthermore, there was no correlation between the ratio and the clinical stage. In protein analysis, we could not find any difference between basic FGF extracted from renal cell carcinomas and that from normal kidney tissues in bioactivity, immunoreactivity, molecular weight and affinity to heparin. On the other hand, anti-basic FGF monoclonal antibody inhibited the growth of a renal cell carcinoma cell line, VMRC-RCW, and this inhibition was reversed by an extraphysiological amount of exogenous basic FGF (100 ng./ml.). These results suggest that basic FGF itself may have no pivotal role in renal cell carcinoma etiology but is involved in the growth of renal cell carcinomas in an autocrine manner.

Animals

Two sialidases which preferentially hydrolyze sialyl alpha 2-8 linkage from Bacteroides fragilis SBT3182.

Bacteroides fragilis SBT3182 produced two sialidases which differ in molecular weight on SDS-PAGE. These sialidases, a 50 kDa and a 55 kDa enzymes, were purified separately and their properties were compared. Both enzymes preferentially hydrolyze sialyl alpha 2-8 linkage rather than alpha 2-3 and alpha 2-6 bonds. The Km values for Neu5Ac alpha 2-3lactose, Neu5Ac alpha 2-6lactose, and colominic acid, which is a homopolymer of N-acetylneuraminic acid linked by alpha 2-8 bonds, were identical between the two enzymes. These enzymes had Km value of 1.0-1.2 mM for Neu5Ac alpha 2-3lactose and 1.3-1.5 mM for Neu5Ac alpha 2-6lactose, which are in the ranges reported for other sialidases. However, the Km values for colominic acid (0.03-0.04 mM) were lower than those of other sialidases, indicating that sialidases from B. fragilis SBT3182 show high affinity for the sialyl alpha 2-8 linkage. The two sialidases also had identical N-terminal amino acid sequences and did not reveal any homology to known sialidases. PAS-staining suggested that these two sialidases were glycoproteins. In the lectin analysis, the 50 kDa enzyme was stained with Con A, DBA, and UEA-I while the 55 kDa sialidase was stained only with Con A. This suggested that the difference in molecular weight may be due to the carbohydrate composition. When the 50 kDa enzyme was incubated with UEA-I, which is a lectin specific for alpha-fucose residue, the activity decreased by 20%.

Amino Acid Sequence

Arachidonic acid-selective cytosolic phospholipase A2 is crucial in the cytotoxic action of tumor necrosis factor.

The role of phospholipase A2 (PLA2) in the cytotoxic action of tumor necrosis factor (TNF) was examined. Recently, we described the characterization of TNF-resistant sublines isolated from TNF-sensitive cell line L929 (Hayakawa, M., Oku, N., Takagi, T., Hori, T., Shibamoto, S., Yamanaka, Y., Takeuchi, K., Tsujimoto, M., and Ito, F. (1991) Cell Struct. Funct. 16, 333-340). The most remarkable features of these TNF-resistant sublines were the defects in TNF-stimulated arachidonate metabolism. In this study, we characterized the PLA2 activities of these sublines and found a significant decrease in the activity in one of the TNF-resistant sublines, C12 cells. The enzymological features, such as Ca2+ requirement and substrate specificity, suggested that the high molecular weight arachidonoyl-selective cytosolic PLA2 (cPLA2) was involved in the TNF action. Northern hybridization analysis demonstrated the reduced expression of high molecular weight cPLA2 in C12 cells. Furthermore, expression of a cloned cPLA2 cDNA in C12 cells increased the sensitivity of cells to the TNF cytotoxicity. These results indicate the crucial role of the high molecular weight cPLA2 in the TNF-induced cytolysis.

Animals

Purification and characterization of a sialidase from Bacteroides fragilis SBT3182.

A sialidase from Bacteroides fragilis SBT3182 was purified 2,240-fold to apparent homogeneity by ammonium sulfate precipitation and sequential chromatographies on DEAE-Toyopearl 650M, Hydroxyapatite, MonoS and Superose6 columns. The N-terminal amino acid sequence of this sialidase, Ala-Asp-X-Ile-Phe-Val-Arg-Glu-Thr-Arg-Ile-Pro-, was determined. Substrate specificity of this enzyme using a variety of sialoglycoconjugates showed a 1.5- and 2.2-fold preference for sialyl alpha 2-8 linkages when compared with alpha 2-3 and alpha 2-6 bound sialic acids, respectively. The native sialidase had a molecular weight of 165kDa, as determined by Superose6 gel filtration chromatography and consisted of three subunits each of 55kDa by SDS-polyacrylamide gel electrophoresis. This enzyme had optimal activity at pH6.1 with colominic acid as substrate.

Amino Acid Sequence

Structure of the bovine ETB endothelin receptor gene.

The structure of the gene encoding the bovine type B endothelin receptor (ETB) has been established and compared with those of other heptahelical receptors. The gene is present as a single copy in the bovine genome, as demonstrated by Southern blot analysis, and spans at least 36 kb. The coding region is divided into 7 exons separated by 6 introns, one of which is more than 23 kb in length. The exons correspond well to the structural domains of the receptor: the first exon encodes the first and second transmembrane domains, and each of the following transmembrane domains is encoded by a separate exon. The portion of the ETB protein sequence encoded by exon 3 is quite different from the corresponding ETA sequence, suggesting that this region is responsible for the distinct ligand specificities of the two receptor subtypes. The second intron interrupts the canonical Asp-Arg-Tyr sequence, which is located at the end of the third transmembrane domain of the heptahelical receptors, as with the substance P, substance K, dopamine D2 and dopamine D3 receptor genes. To map the 5' region of the gene and determine the start of transcription, primer-extended cDNAs were cloned and sequenced: multiple start sites were deduced with no apparent TATA box in the expected upstream region. Similar results were obtained by ribonuclease protection analysis.

Animals

Primary structure of the human elafin precursor preproelafin deduced from the nucleotide sequence of its gene and the presence of unique repetitive sequences in the prosegment.

The human elafin gene was cloned and its entire nucleotide sequence was determined to deduce the amino acid sequence for the precursor of elafin, an elastase-specific inhibitor. The gene spans approximately 1.7 kb and is divided into 3 exons. The gene product preproelafin consists of 117 amino acids: the initiator Met, a putative 25-amino acid signal peptide, a pro-sequence of about 34 amino acids, and the C-terminal 57 amino acids for mature elafin. Possible covalent clotting of the prosegment and its physiological significance have been pointed out based on a remarkable sequence similarity between the pro-sequence and the guinea pig seminal clotting protein SVP-1.

Amino Acid Sequence

The thickness of the sound and periodontally diseased human cementum.

Cementum of teeth previously analysed for fluoride was re-examined in order to determine whether or not periodontal disease had affected the thickness of the tissue. In the periodontally diseased teeth the cementum was thinner than normal in the middle region of the root. The apical cementum, however, was significantly thicker in periodontally diseased than in the sound teeth of subjects over 60 yr old. This may account for the higher total fluoride levels previously reported in the apical cementum of these same teeth.

Adult

Liposomal modification with uronate, which endows liposomes with long circulation in vivo, reduces the uptake of liposomes by J774 cells in vitro.

For overcoming rapid removal of liposomes from the bloodstream, we developed reticuloendothelial system (RES)-avoiding liposomes modified with a uronic acid derivative, palmityl-D-glucuronide (PGlcUA). In this current study, we examined the in vitro interaction of PGlcUA-liposomes with J774 cells derived from mouse macrophages. Liposomal association with J774 cells at 37 degrees C did not increase compared with the binding at 4 degrees C when liposomes were modified with PGlcUA. RES-avoiding ability was not specifically endowed by glucuronate but by uronates in general, since palmityl-D-galacturonide showed a similar effect on liposomal clearance in vivo and liposomal uptake in vitro. These facts indicate that modification of the liposomal surface with uronic acid derivatives endows liposomes with a long circulation time in the bloodstream by reducing their uptake by macrophages.

Animals

Transient, unilateral, isolated hypoglossal nerve palsy.

We report a boy with isolated hypoglossal nerve palsy that recovered within twelve weeks. Investigations of the cervix, base of the skull, medulla and hypoglossal nerve by CT-scan and MRI did not show any abnormal findings. There are a few reports concerning isolated unilateral hypoglossal nerve palsy with benign course. Although we could not establish the cause of our patient's disease, an awareness of this condition should save such patients from unnecessary invasive studies.

Child

[Clinical studies on pediatric purulent meningitis--clinical symptoms and prognosis].

In 149 patients with purulent meningitis we encountered in the period of 20 years from 1970 to 1990, their clinical symptoms and prognosis were investigated. Death or sequela was noted in many of the patients having loss of consciousness, stiffness of the members and/or cyanosis as primary clinical symptoms, or having hypoalbuminemia (less than 2.5 g/dl) and/or thrombocytopenia as abnormal laboratory findings, or having excessive protein levels and/or excessively low sugar levels in cerebro-spinal fluid. Early initiation of adequate antibiotic therapy, as well as symptomatic treatment using transfusion, steroids and anticonvulsants, are important.

Female