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Biomedical subjects

I Kato

Publications and source records attributed to I Kato.

At least 451 records · Page 25Linked to original sources

Isolation and functional expression of pituitary peptidylglycine alpha-amidating enzyme mRNA. A variant lacking the transmembrane domain.

We demonstrate that, in rat pituitary, peptidylglycine alpha-amidating enzyme was encoded by at least 5 distinct mRNAs. Southern blot and ribonuclease protection analyses revealed that the mRNAs arose through alternative splicing. A variant lacking the transmembrane domain-coding sequence was a major mRNA species for the enzyme in the pituitary. When the cDNAs were expressed in COS-7 cells, the variant was the most efficient in producing a secretory form (37 kDA) of the enzyme.

Amino Acid Sequence↗

Modulation of haptotactic migration of metastatic melanoma cells by the interaction between heparin and heparin-binding domain of fibronectin.

We utilized recombinant fibronectin polypeptides with cell-binding domain and heparin-binding domains (referred to as C-274 and H-271, respectively) and their fusion polypeptide (CH-271) to examine the role of sulfated polysaccharide heparin and/or the functional domains of fibronectin in modulating tumor cell behavior. Both C-274 and CH-271 polypeptides with cell-binding domains promoted the adhesion and migration of B16-BL6 melanoma cells, whereas H-271 did not. Heparin bound to the immobilized polypeptides with heparin-binding domain (H-271, CH-271, and a mixture of C-274 and H-271 or fibronectin) but did not affect the tumor cell adhesion to the substrates. At the same time, heparin or two monoclonal antibodies against the heparin-binding domain were able to inhibit the haptotactic migration to CH-271 or fibronectin, though not to C-274 or a mixture of C-274 and H-271. This suggests that although heparin did not affect tumor cell adhesion to the cell-binding domain near the heparin-binding domain in CH-271 or fibronectin, it did lead to a modulation of cell motility. It seems likely that the regulatory mechanism may depend on interaction between heparin-like molecules on the cell surface and the heparin-binding domain in fibronectin, rather than on simple steric hindrance or on the masking of the cell-binding domain caused by the binding of heparin to heparin-binding domain.

Animals↗

Primary structure of the heparin-binding site of type V collagen.

The abilities of collagens, type I, II, III, IV, and V, to bind heparin were examined by heparin-affinity chromatography and binding studies with [35S]heparin. At a physiological pH and ionic strength, only type V collagen bound to heparin. Collagens type I and II showed higher affinities than types III and IV for heparin, but did not bind to a heparin column at a physiological ionic strength. The heparin binding site of type V collagen was located in a 30 kDa CNBr fragment of the alpha 1(V) chain, and the amino acid sequence of this fragment was determined. The 30 kDa fragment contained a cluster of basic amino acid residues, and enzymatic cleavage within this basic domain greatly reduced the heparin-binding activities of the resulting peptides. Thus this basic region is probably the heparin-binding site of type V collagen.

Amino Acid Sequence↗

Amplified and rearranged bcl-2 gene in two lymphoma cell lines, FL-218 and FL-318, carrying a 14;18 translocation.

Two human B-cell lines carrying a 14;18 chromosome translocation [t(14;18)(q32;q21)], designated FL-218 and FL-318, were established from effusion cells of two Japanese patients manifesting the transformed histology of follicular lymphoma. The FL-218 and FL-318 cell lines were composed of cells in the hyperdiploid range, which had two and three or four 18q- chromosomes, respectively. These 18q- chromosomes were not distinguishable from an 18q- chromosome derived from t(14;18) since they exhibited the same banding pattern. Southern blot analysis revealed that in both cell lines, breakage of the bcl-2 gene occurred within the major breakpoint cluster region and the truncated gene juxtaposed to an immunoglobulin heavy chain gene locus. The autoradiographic intensity of the retained fragment each on 18q- chromosome was more enhanced than that of the translocated fragment on 14q+ chromosome. These findings suggest that the extra 18q- chromosome found in t(14;18)-positive cancer does not arise from de novo independent t(14;18) but from duplication of a preexisting 18q- chromosome.

Aged↗

Activation of phospholipase A2 in rabbit erythrocyte membranes by a novel hemolytic toxin (H-toxin) of Clostridium septicum.

A primary effect of a novel H-toxin of Clostridium septicum on the hemolysis of rabbit erythrocytes was shown to be the activation of phospholipase A2 (PLA2) associated with rabbit erythrocyte membranes by 20-fold that of controls. Furthermore, the activation of PLA2 induced by the H-toxin was enhanced in the presence of NAD. The H-toxin itself had no PLA2 activity. On the contrary, the H-toxin bound to palmitic acid at a molar proportion of 1:1 and lost its hemolytic activity. The PLA2 was not activated by the H-toxin bound to palmitic acid. These results suggest that activation of the PLA2 is responsible for development of the hemolytic activity of the H-toxin.

Animals↗

Increased vascular permeability, erythema, and leukocyte emigration induced in rabbit skin by streptococcal erythrogenic toxin type A.

A highly purified streptococcal erythrogenic toxin type-A (SET-A) caused increased vascular permeability, erythema, and leukocyte emigration when injected into the skin of rabbits. A blueing reaction indicating increased vascular permeability appeared at 1 h, reaching the highest intensity between 4 and 5 h, decreasing thereafter and completely disappearing at 12 h after toxin injection. The intensity of the increase in permeability was found to be dose dependent. The erythematous reaction began later and persisted longer than the blueing. The time course of leukocyte emigration was found roughly to parallel that of the blueing reaction. The skin reaction to SET-A in rabbits can be characterized as having an acute non-specific exudative inflammatory nature.

Animals↗

Characterization of a functional domain of human calpastatin.

Expression plasmids were constructed from the cDNA of human calpastatin to examine the contribution to the inhibition of calpain of highly conserved sequences in each of four repetitive domains. A series of deletion derivatives of domain 1 proteins, truncated at either the amino or carboxy terminus, were produced in E. coli. Deletion from the amino terminus past the amino terminal conserved sequence decreased the inhibition. When the middle conserved sequence, the M-sequence, was further deleted, no inhibition was detected, but deletion from the carboxy terminus past the carboxy terminal conserved sequence did not decrease the inhibition until the M-sequence was reached. Nuclear magnetic resonance and circular dichroism spectra showed that domain 1 has an unfolded structure. Peptides that contained the M-sequence and some neighboring sequences were synthesized to measure the minimum size of the inhibitory peptide, which was the M-sequence with the next six residues on the amino terminal side.

Amino Acid Sequence↗

Effects of recombinant murine interferon-gamma on pregnant mice and their fetuses.

Recombinant murine interferon-gamma (Rec-MuIFN-gamma) was administered intramuscularly to C3H/HeNCrj mice on Days 6-15 of gestation at dosage levels of 8 X 10(5), 4 X 10(6), and 2 X 10(7) u/kg/day. Dams were killed for examination of fetuses on Day 18 of gestation. Pregnant females that received 2 X 10(7) u/kg/day of Rec-MuIFN-gamma showed uterine bleeding on Days 10-15 of gestation and could not maintain their pregnancy. These dams died on Days 13-17 or were killed in extremis on Days 10-15 for examination, and therefore no fetal data were available for this group. In the 2 X 10(7) u/kg/day group, the mean absolute weights of the lung and spleen increased and the mean absolute weight of the liver, red blood cells (RBC), hematocrit, and hemoglobin decreased significantly. Surviving dams in the 8 X 10(5) and 4 X 10(6) u/kg/day groups showed significant increases in the mean absolute weights of the lung, liver, kidneys, and spleen and a decrease in platelet count. Significant increases in the weights of the heart and ovaries and decreases in RBC, hematocrit, and hemoglobin were observed in the 4 X 10(6) u/kg/day group. Histopathological examination revealed increased extramedullary hematopoiesis in the spleen of the 4 X 10(6) and 2 X 10(7) u/kg/day groups. Fetuses showed no external, visceral, or skeletal malformations and variations caused by the administration of Rec-MuIFN-gamma in any of the treated groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Papillary eccrine adenoma. Immunohistochemical and ultrastructural analyses.

A case of papillary eccrine adenoma was analysed with immunohistochemical and ultrastructural methods regarding their direction of differentiation. It was found that the majority of the structures show either eccrine ductal or glandular differentiation. There were some segments, particularly in those exhibiting papillary growth, where cells similar to eccrine secretory (clear) cells or cells with characteristics of both ductal basal cells and glandular myoepithelial cells were present.

Carcinoembryonic Antigen↗

Tracheostomy--the horizontal tracheal incision.

The complication rate after emergency tracheostomy is two to five times greater than after elective procedures. One of the main causes of the high risk of complications in emergency tracheostomy appears to be the amount of time required to open the trachea. Therefore, simple and fast procedures are mandatory. We have developed a new procedure as follows: A horizontal skin incision is performed. Strap muscles are dissected and retracted laterally. A transverse cut between tracheal rings below the thyroid isthmus is performed up to membranous portion of the trachea. The cut ends of the trachea remain open naturally because of the elasticity of the trachea. Skin and tracheal cut-ends are then joined by interrupted sutures. We have used this procedure during the past three years and have not experienced any major complications. This demonstrates the clear advantage and the more physiological nature of the procedure over various other incisions of the tracheal wall.

Adult↗

Mapping of brainstem lesions by the combined use of tests of visually-induced eye movements.

To determine the diagnostic value of visually-induced eye movements for indicating the lateralization of the lesion, optokinetic nystagmus (OKN), fixation-suppression of caloric nystagmus and pursuit eye movements were investigated in 28 patients who showed discrete unilateral brainstem lesions. In all patients, pursuit gains decreased in parallel with the direction of the impairment of slow-phase OKN velocity with a significant left/right difference. Decreases of gains were predominantly towards the affected side in 22 patients, whereas they were predominantly towards the contralateral side in 2 patients with dorsal tegmental pontine lesions and in 4 out of 8 patients with Wallenberg's syndrome. The relationship of pursuit gains to percentage reduction of fixation-suppression of caloric nystagmus (%FS) showed no correlation. The following four groups were classified. In group A, which was the largest, pursuit gains and %FS decreased predominantly towards the lesioned side. This group consisted of 5 patients with lesions in the midbrain, 6 patients with lesions in the ventral pons and 4 out of 8 patients with Wallenberg's syndrome. The opposite of group A was group D, showing reverse electro-oculographic (EOG) patterns to those in group A in relation to the lesioned side. Group D consisted of 2 patients with lesions in the dorsal pontine tegmentum. This observation, taken together with the decreases of pursuit and OKN gains in relation to the lesioned side, might indicate that lesions of ascending fibres are responsible for pursuit and OKN abnormalities. Group B, consisting of 7 patients with lesions either in the superior or middle cerebellar peduncles, showed decreased pursuit gains predominantly towards the lesioned side and %FS reduced predominantly towards the side contralateral to the lesion. EOGs of these patients were consistent with the results of floccular ablation in the monkey. In group C, these two parameters showed patterns opposite to those in group B in relation to the lesioned side and this group consisted of the other 4 patients with Wallenberg's syndrome. In patients of this group, the inferior cerebellar peduncle might be involved. The combined use of these tests is thus useful for lateralizing the lesion in the brainstem.

Brain Diseases↗

Characterization of hemoglobin-hydrolyzing acidic proteinases in human and rat neutrophils.

The nature and levels of hemoglobin (Hb)-hydrolyzing acidic proteinases including cathepsin D and cathepsin E, which were most active at pH 3.5-4.0, were enzymatically and immunochemically compared between human and rat neutrophils. By subcellular fractionation and immunoprecipitation with discriminative antibodies specific for each enzyme, cathepsin D was shown to be present in the granular content fraction of both human and rat neutrophils and to account for about 35% of the total Hb-hydrolyzing activity. Cathepsin E was observed mainly in the cytoplasmic fraction of rat neutrophils from peripheral blood and peritoneal exudates and accounted for about 65% of the total activity, but it was not detected in human blood neutrophils. Immunoelectron microscopy on rat neutrophils revealed that cathepsin D was exclusively confined to lysosomes, whereas cathepsin E was localized mainly in the cytoplasmic matrix and often in the perinuclear spaces and the rough endoplasmic reticulum. The non-cathepsin D activity in human neutrophils, which represented about 65% of the total activity, appeared to be due to a serine proteinase, since it was inhibited by diisopropyl fluorophosphate and phenylmethylsulfonyl fluoride and was not inhibited by agents specific for aspartic-, cysteine-, or metallo proteinases. The enzyme(s) responsible for this activity was largely associated with the granular membranes, and a half of it could be described as an integral membrane protein on the basis of phase separation with Triton X-114 at 35 degrees C. The levels of these Hb-hydrolases in gingival crevicular fluid from human chronic inflammatory periodontitis patients were examined in order to clarify their participation in the periodontal tissue breakdown.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

An epidemiological study on occupation and cancer risk.

The relation between occupation and cancer risk was examined on the basis of 17,164 male and 6,835 female cancer patients aged 30 years or over who were entered in the Aichi Cancer Registry during the period, 1979-1987. Controlling for age, the risk of developing lung cancer was significantly high in sales, transport-and-communications, mental, ceramics and construction workers in men, and service workers in women. The risk of developing liver cancer was significantly high in transport-and-communications and service workers in men. The risk of developing colon cancer was significantly high in professional people of both sexes and in clerical workers in men. The risk of developing female breast cancer was significantly high in professional women, administrative and clerical workers and hairdressers. The risk of developing stomach cancer was significantly high in male and female agricultural workers, while that of developing cancer of the mouth-and-pharynx was significantly high in construction workers in men and filature-and-spinning workers in women. Analysis of smoking and alcohol drinking habits, by occupation, suggested the increased risk of developing lung cancer to be associated with a greater percentage of smokers and the increased risks of developing cancers of the liver and mouth-and-pharynx to be associated with a greater percentage of daily alcohol drinkers. When the analysis was limited to smokers, the risk of developing lung cancer was still significantly high in metal, ceramics and construction workers in men.

Alcohol Drinking↗

The polymerase chain reaction for Mycoplasma pulmonis.

In vitro DNA amplification by polymerase chain reaction was examined to detect Mycoplasma pulmonis. A pair of synthetic oligonucleotide primers was constructed, and used to amplify a unique sequence of M. pulmonis DNA. Amplified products were detected by agarose gel electrophoresis and verified by blot hybridization with a synthetic oligonucleotide probe. This system detected cellular DNA of M. pulmonis but not M. arthritidis or M. neurolyticum, and thus appears to be useful for M. pulmonis diagnosis.

Base Sequence↗

Amplification and specific detection of transforming gene region of human papillomavirus 16, 18 and 33 in cervical carcinoma by means of the polymerase chain reaction.

We have established a highly sensitive method for specific detection of human papillomavirus (HPV) 16, 18 and 33, by using the polymerase chain reaction (PCR). A HPV-related sequence (140 bp) in the E6 transforming region was specifically amplified and detected by gel electrophoresis and by the use of a specific oligonucleotide probe. The PCR could detect 10(5)-10(6) copies per cell (maximum sensitivity). Furthermore, HPV 16, 18 and 33 DNAs were synthesized in a common reaction solution and specifically detected by HPV type-specific probes. The PCR detected the HPV sequence from tissues which were negative to Southern hybridization. This detection technique may contribute significantly to the precise analysis of HPV in small proliferative lesions in the cervix.

Base Sequence↗

A comparative case-control study of colorectal cancer and adenoma.

We conducted a comparative case-control study of colorectal cancer and adenoma involving 221 cases with colorectal cancer, 525 cases with colorectal adenoma and 578 neighborhood controls. Daily vegetables intake was associated with lower risks of distal colon adenoma (relative risks (RR) = 0.59, 95% confidence interval (CI): 0.39-0.89) and rectal cancer (RR = 0.46, 95% CI: 0.25-0.84). Daily beans intake was associated with lower risk of colon adenoma (RR = 0.58, 95% CI: 0.37-0.91 for the proximal colon and RR = 0.63, 95% CI: 0.45-0.88 for the distal colon) and daily intake of seaweeds was associated with lower risk of rectal cancer (RR = 0.42, 95% CI: 0.22-0.82). Daily intake of fish and shellfish also showed an inverse association with the risk of colon adenoma (RR = 0.67, 95% CI: 0.45-0.99 for the proximal colon and RR = 0.70, 0.52-0.94 for the distal colon). Generally, intakes of animal or vegetable fat-rich foods, especially meats, were associated with decreases in risks of both adenoma and cancer, though the association of cancer was not statistically significant. Other than dietary factors, daily alcohol drinking was associated with an increased risk of adenoma in the proximal colon (RR = 1.95, 95% CI: 1.15-3.29) and ex-drinkers showed higher risks for colon adenoma and colorectal cancer. Sports or occupational activities and coffee drinking were inversely associated and family history of colorectal cancer was positively associated with the risk of both colorectal adenoma and cancer.

Adenoma↗

A case-control study of male colorectal cancer in Aichi Prefecture, Japan: with special reference to occupational activity level, drinking habits and family history.

The relationships of occupational activity level, drinking habits and family history of cancer to the risk of male colorectal cancer by subsites were investigated in a case-control study involving 1,716 cases with colon cancer, 1,611 cases with rectal cancer and 16,600 controls with other sites of cancer identified from the Aichi Cancer Registry, Japan 1979-1987. An occupation with a low activity level was associated with an increased risk of colorectal cancer; the age-adjusted relative risk (RR) compared to the high activity level group was 1.92 (95% confidence interval (CI): 1.38-2.67) for proximal colon cancer, 1.52 (95% CI: 1.19-1.94) for distal colon cancer and 1.38 (95% CI: 1.17-1.62) for rectal cancer. Beer drinkers showed an increased risk of colorectal cancer; the age-adjusted RR was 1.49 (95% CI: 1.13-1.95) for proximal colon cancer, 1.65 (95% CI: 1.34-2.04) for distal colon cancer and 1.88 (95% CI: 1.62-2.18) for rectal cancer. The RR for family history of colorectal cancer was 3.40 (95% CI: 2.19-5.29) for proximal colon cancer, 2.54 (95% CI: 1.73-3.75) for distal colon cancer and 1.78 (95% CI: 1.28-2.49) for rectal cancer. Multivariate analysis controlled for age, residence, marital status and smoking in addition to occupational activity level, beer drinking and family history of colorectal cancer did not materially change the RRs. When these three variables were combined, the RR was 15.72 (95% CI: 5.40-45.78) for proximal colon cancer, 10.55 (95% CI: 4.24-26.27) for distal colon cancer and 6.69 (95% CI: 3.12-14.36) for rectal cancer.

Adult↗

Inhibition of lung metastasis by synthetic and recombinant fragments of human fibronectin with functional domains.

We have investigated the antimetastatic effect of synthetic or recombinant peptides containing the functional domains of fibronectin on experimental and spontaneous lung metastases of murine tumor cells. CS1 peptide which is present within type III homology connecting segment (IIICS) as well as C-274 (cell-binding domain) were able to inhibit experimental lung metastasis when co-injected intravenously (iv) with B16-BL6 melanoma cells, while H-271 (heparin-binding domain) could not. In the spontaneous metastasis model, multiple iv administrations of CS1 or C-274 after surgical excision of primary tumors caused a significant reduction of metastatic colonies in the lung. Both CS1 and C-274 significantly inhibited cell adhesion and migration to fibronectin-coated substrates when added freely in solution. CS1 peptide also inhibited the cell adhesion and migration to laminin-coated substrates, but C-274 did not. H-271 did not have any inhibitory effect on cell adhesion or migration to either of the substrates. Similarly, CS1 inhibited tumor invasion to both Matrigel/fibronectin- and Matrigel/laminin-coated filters, whereas C-274 inhibited the invasion to only Matrigel/fibronectin-coated filter. These results indicate that CS1 peptide of fibronectin, lacking the Arg-Gly-Asp-containing domain, actively inhibits tumor metastases in spontaneous and experimental metastasis models. The use of such a peptide might offer a promising therapeutic approach for combatting or preventing cancer metastasis.

Amino Acid Sequence↗