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Biomedical subjects

S Ohno

Publications and source records attributed to S Ohno.

At least 775 records · Page 43Linked to original sources

Clinicopathologic study of early stage esophageal carcinoma.

As part of a consecutive series of 370 patients who underwent subtotal esophagectomy because of carcinoma of the thoracic area of the esophagus, between January 1965 and July 1988, in the Second Department of Surgery, Kyushu University Hospital, 42 patients (11.4%) with early stage esophageal carcinomas confined to the intraepithelium, mucosa, or submucosa were studied clinicopathologically. Of these 42, 26 (61.9%) had symptoms; slight dysphagia or chest discomfort was the most common symptom. The remaining 16 (38.1%) had no subjective symptoms. Endoscopic examination proved to be more useful than barium studies. Lugol-combined endoscopy was most effective in detecting the presence and spread of small malignant lesions of the esophagus. At the time of surgery, six patients with submucosal carcinoma of the esophagus had lymph node metastasis, and five died of recurrence. Described herein are the diagnostic features, clinicopathologic characteristics, and long-term results of these 42 patients with early stage, and 328 patients with advanced, carcinomas of the esophagus, detected and surgically treated in our clinics.

Actuarial Analysis↗

[Hyperthermo-chemo-radiotherapy of patients with carcinoma of the esophagus and prediction of the clinical remedial value using the in vitro succinate dehydrogenase inhibition test].

Hyperthermia combined with irradiation and chemotherapy was prescribed for patients with resectable (n = 88) and unresectable (n = 36) carcinoma of the esophagus. The histopathological effectiveness, and the long term results were compared between two groups of patients treated with hyperthermo-chemo-radiotherapy (HCR therapy) and those treated with chemoradiotherapy (CR therapy). A correlation between the hyperthermia sensitivity test, using the in vitro succinate dehydrogenase inhibition test, and the clinical remedial value was also examined in malignant tissues from 47 patients with esophageal cancer, and treated with HCR therapy. In the resected cases, preoperative HCR therapy resulted in a significantly higher histopathological effectiveness rate (69%) compared with that in cases treated by CR therapy (48%) (P less than 0.05). The long term results of patients with both resectable and unresectable carcinoma, given HCR therapy were significantly better than those given CR therapy (P less than 0.05). On the other hand, the clinical remedial value, determined radiographically showed a correlation rate of 77% to the hyperthermia sensitivity test. Thus, the HCR therapy resulted in not only a higher histopathological effectiveness rate but also a significantly longer survival without severe side effects, and this hyperthermia sensitivity test using the succinate dehydrogenase inhibition test facilitates prediction of the outcome of the HCR therapy.

Antineoplastic Agents↗

[Studies on HLA system of family members with Behçet's disease].

In order to investigate the immunogenetic mechanism of Behçet's disease, frequencies of HLA antigens were studied in family members of patients with this disease. The subjects consisted of 37 patients, 74 family members and 49 normal controls. It was shown that the frequencies of HLA-B51 were equally higher in the patients, fathers, mothers and siblings of the patients than in the normal controls. On the other contrary, the frequency of HLA-DQw1 was significantly decreased only in the patients with this disease. These results may suggest that family members of the patients have resistant genetic factors, unlike the patients.

Behcet Syndrome↗

[A case of pseudohypoparathyroidism type 1 with systemic lupus erythematosus].

A case of pseudohypoparathyroidism (PHP) type 1 with systemic lupus erythematosus (SLE) is reported. A 36-year-old women was admitted to our hospital with the complaints of dyspnea, arthralgia, tetany and tremor. Laboratory findings on admission showed; leukopenia, thrombocytopenia, hypocalcemia, positive antinuclear, anti-RNP, anti-Sm antibodies. A diagnosis of PHP type 1 was made from the findings of Albright's osteodystrophy and Ellsworth-Howard test. On the basis of various auto antibodies and clinical findings, the patient was diagnosed as SLE, too. She was started on a therapy of prednisolone at a dose of 40 mg per day. Her clinical manifestations immediately became better, and her laboratory findings subsequently improved. Up to the present, the case report of overlapping syndrome of PHP type 1 and SLE is very rare. Both PHP and SLE were considered to be in a category of autoimmune disease and the relationship between PHP and SLE was discussed.

Adult↗

Molecular cloning of the cDNA for the large subunit of the high-Ca2+-requiring form of human Ca2+-activated neutral protease.

A nearly full-length cDNA clone for the large subunit of high-Ca2+-requiring Ca2+-activated neutral protease (mCANP) from human tissues has been isolated. The deduced protein, determined for the first time as an mCANP, has essentially the same structural features as those revealed previously for the large subunits of the low-Ca2+-requiring form (muCANP) [Aoki, K., Imajoh, S., Ohno, S., Emori, Y., Koike, M., Kosaki, G., & Suzuki, K. (1986) FEBS Lett. 205, 313-317] and chicken CANP [Ohno, S., Emori, Y., Imajoh, S., Kawasaki, H., Kisaragi, M., & Suzuki, K. (1984) Nature (London) 312, 566-570]. Namely, the protein, comprising 700 amino acid residues, is characterized by four domains, containing a cysteine protease like domain and a Ca2+-binding domain. The overall amino acid sequence similarities of the mCANP large subunit with those of human muCANP and chicken CANP are 62% and 66%, respectively. These values are slightly lower than that observed between muCANP and chicken CANP (70%). Local sequence similarities vary with the domain, 73-78% in the cysteine protease like domain and 48-65% in the Ca2+-binding domain. These results suggest that CANPs with different Ca2+ sensitivities share a common evolutionary origin and that their regulatory mechanisms are similar except for the Ca2+ concentrations required for activation.

Amino Acid Sequence↗

Coexistence of intraepithelial carcinoma and glandular differentiation in esophageal squamous cell carcinoma.

A review of 249 cases of squamous cell carcinoma of the esophagus showed 77 cases (30.9%) with intraepithelial carcinoma contiguous to the main lesion. There were 48 cases (19.3%) with glandular and/or mucus-secreting components, in addition to the usual components of squamous cell carcinoma. Coexistence of intraepithelial carcinoma was observed in 20 cases (41.7%) among 48 with glandular differentiation, as compared with 57 cases (28.4%) without this differentiation. Of the 20 cases with glandular differentiation without preoperative irradiation, there were 16 (80.0%) containing areas of intraepithelial carcinoma. Moreover, among 77 cases with intraepithelial carcinoma, 20 (26.0%) were accompanied by glandular differentiation. Of nine tumors restricted to the mucosal or submucosal layer in 48 cases with glandular differentiation and in 44 of 203 cases without such differentiation, there were eight cases (88.9%) and 31 cases (70.5%) containing the areas of intraepithelial carcinoma, compared with rates of 30.8% and 16.6%, respectively, in the advanced carcinomas. Therefore, in the early carcinomas with glandular differentiation, there often coexist intraepithelial carcinomas. This high incidence of the coexistence of intraepithelial carcinoma and glandular differentiation, particularly in early cancers, supports the theory of a field carcinogenesis of esophageal carcinomas.

Adenocarcinoma↗

Increased degradation of protein kinase C without diminution of mRNA level after treatment of WEHI-231 B lymphoma cells with phorbol esters.

Immunoblot analysis of WEHI-231 B lymphoma cell homogenates revealed that both type II, a major component, and type III, a minor component, protein kinase C (PKC) were present. Northern blot analysis of PKC mRNA showed a higher level of beta II and beta I mRNA (encoding type II PKC) than of alpha mRNA (encoding type III PKC). Short term (3 min) treatment with phorbol 12-myristate 13-acetate (PMA) caused a rapid loss of PKC in cytosol and a concomitant increase in the particulate fraction. After prolonged (24 hr) exposure, the level of both PKC isozymes were decreased. However, the corresponding mRNA levels remained intact. PMA did not inhibit the anti-IgM-mediated increase in [Ca2+]i in PKC-depleted cells.

Animals↗

Lipoprotein cholesterol concentrations in patients with Behçet's disease.

Serum cholesterol concentrations among very low, low, and high density lipoproteins (VLDL, LDL and HDL) in 12 male patients with Behçet's disease were compared with those of 12 normal male subjects. Serum lipoproteins were separated by a combination of ultracentrifugation and gel filtration chromatography. The patients had significantly (p less than 0.001) lower concentrations of HDL-cholesterol than the control subjects (356 +/- 62 mg/l vs. 573 +/- 108 mg/l, means +/- SD). The cholesterol concentrations in apolipoprotein B-containing lipoproteins (VLDL and LDL) from the patients tended to be reciprocally higher than those of the controls, though not statistically significant. There was no difference in serum total cholesterol concentrations. The chemical composition of HDL from the patient group was characterized by higher protein and lower cholesterol (both esterified and free) contents compared with the control HDL.

Adult↗

A novel phorbol ester receptor/protein kinase, nPKC, distantly related to the protein kinase C family.

Protein kinase C (PKC)-related cDNA clones encode an 84 kd protein, nPKC. nPKC contains a cysteine-rich repeat sequence homologous to that seen in conventional PKCs (alpha, beta I, beta II, and gamma), which make up a family of 77-78 kd proteins with closely related sequences. nPKC, when expressed in COS cells, confers increased high-affinity phorbol ester receptor activity to intact cells. Antibodies raised against nPKC identified a 90 kd protein in rabbit brain extract as well as in extracts from COS cells transfected with the cDNA construct. nPKC shows protein kinase activity that is regulated by phospholipid, diacylglycerol, and phorbol ester but is independent of Ca2+. The structural and enzymological characteristics of nPKC clearly distinguish it from conventional PKCs, which until now have been the only substances believed to mediate the various effects of diacylglycerol and phorbol esters. These results suggest an additional signaling pathway involving nPKC.

Amino Acid Sequence↗

Serial histologic evaluation of multiple primary squamous cell carcinomas of the esophagus.

A review of data on 205 patients with esophageal squamous cell carcinoma who underwent subtotal esophagectomy revealed 30 cases (14.6%) and 32 lesions with multiple primary squamous cell carcinomas. The incidence of this multiplicity was 11.7% and 25.6% in those with and without preoperative irradiation treatment, respectively. Among the 32 second lesions, there were 17 intraepithelial carcinomas, eight restricted to the mucosa, five invading the submucosa, one invading down to the proper muscular layer, and one involving the entire thickness of the esophageal wall. These second lesions were in the relatively early stage. Moreover, incidence of the coexistence of intraepithelial carcinoma contiguous to the main lesion was 42.1% and 100.0% in those with multiple cancers, with and without preoperative irradiation, respectively. The values were 7.6% and 53.1% in patients with a solitary carcinoma, respectively. These findings show the close relationship between multiplicity and intraepithelial carcinoma contiguous to the main lesion, and support the concept of multicentric or field carcinogenesis of esophageal squamous cell carcinoma.

Adenocarcinoma↗

An atypical t(12;15) translocation of chromosomes found in murine plasmacytomas and activation of the c-myc oncogene.

Cells from murine plasmacytomas (MPC) consistently exhibit either the 12;15 or the 6;15 translocation. Recently, we found that cells from 2 MPC (ABPC 45 and ABPC 26) did not exhibit any known translocation. However, these MPC contained one chromosome 15 (15q-) that was shorter than its normal homologue and one 12 (12q+) that was longer than its normal 12 counterpart. Chromosome 15q- contained only one thin D band, corresponding in size to either D1 or D3 band. A minor light band D2 was apparently deleted. Chromosome 12q+ contained a light F1 band that was longer than the normal 12F1. In ABPC 45, the c-myc gene was assigned by in situ hybridization to the F1 region of 12q+ as well as to its original site of 15D2. Moreover, the in situ hybridization experiment assigned the S alpha gene to the F1 regions of both chromosomes 12 and 12q+. These findings indicate that a minor light band D2 of chromosome 15 carrying the c-myc gene was translocated into the major light band F1 of 12, resulting in a longer chromosome 12q+ and a correspondingly shorter chromosome 15q-. This type of chromosomal translocation suggests that ABPC 45 developed through a cytogenetic mechanism different from that of MPC with the typical t(12;15) translocation.

Animals↗

A fourth type of rabbit protein kinase C.

Three rabbit cDNA clones coding for three types of protein kinase C (PKC alpha, beta, and gamma) have recently been identified and the structures determined [Ohno, S., Kawasaki, H., Imajoh, S., Suzuki, K., Inagaki, M., Yokokura, H., Sakoh, T., & Hidaka, H. (1987) Nature (London) 325, 161-166]. By use of these cloned cDNAs as hybridization probes, a fourth type (delta) of cDNA clone, which encodes a protein highly homologous to PKC alpha, beta, and gamma, was identified. PKC delta is composed of 697 amino acid residues and contains several peptide sequences determined at the protein level with the brain PKC preparation. This indicates that this molecular type (PKC delta) is, along with PKC alpha, beta, and gamma, a constituent of the brain PKC preparation. Sequence comparison among the four PKC types revealed that PKC delta is somewhat distinct from the other PKC types. PKC delta shows 99% amino acid sequence identity with rat PKC type I [Knopf, J. L., Lee, M.-H., Sultzman, L. A., Kriz, R. W., Loomis, C. R., Hewick, R. M., & Bell, R. M. (1986) Cell (Cambridge, Mass.) 46, 491-502], indicating relationship of these PKC types. The mRNA for PKC delta is exclusively concentrated in the brain.

Amino Acid Sequence↗

Expression of human leukotriene A4 hydrolase cDNA in Escherichia coli.

The cDNA clone encoding human leukotriene A4 hydrolase was inserted into a vector pUC9 and expressed in Escherichia coli as a fusion protein containing the first 10 amino acid residues derived from a vector. The leukotriene A4 hydrolase activity was recovered in the soluble fraction of the transformants. The purified enzyme showed kinetic properties similar to the native enzyme, including inactivation by the substrate and sulfhydryl-modifying reagents. The results demonstrate that a protein with an Mr of 70,000 was expressed in Escherichia coli with a full enzyme activity and structural fidelity. Acquisition of the expression system makes it feasible to elucidate the reaction mechanism of the enzyme.

Cloning, Molecular↗

Multivariate approach for assessing the prognosis of clinical oesophageal carcinoma.

We investigated the prognostic contribution of 15 discrete variables on the survival of 123 patients with carcinoma of the oesophagus who underwent oesophagectomy and oesophageal reconstruction. In the multivariate analysis, three of fifteen variables were associated with the prognosis of patients who underwent oesophagectomy. The variables are: resectability of the malignant lesion, DNA distribution pattern of the cancer cells and postoperative complications. The DNA distribution pattern proved to be one of the most reliable prognostic factors. These three variables were assigned one of two values, 'favourable' or 'unfavourable', indicative of the effect on survival. The 123 patients were classified into four groups, characterized by eight possible combinations of these three variables. The survival rate of those with two or more 'favourable' variables was the highest, that is about 50 per cent at 5 years after surgery. On the other hand, patients with two or more 'unfavourable' variables had a very poor prognosis. Therefore, early detection and postoperative care play key roles in determining the survival of patients with oesophageal carcinoma.

Adult↗

Regulation of activity of calcium activated neutral protease.

Various lines of evidence suggest that calcium dependent protease (CANP, calpain) exists in the cytosol as an inactive proenzyme which is converted to an active form by autolysis. During autolysis only the N-terminal regions of both subunits of proCANP are modified. About 20 and 90 residues are removed from the large and small subunits, respectively. The N-terminal region (domain I) of the large subunit modified during autolysis precedes the protease domain and corresponds to the propeptides of various cysteine proteinases. Analyses of the autocatalytic activation of CANP in the presence of plasma membranes reveal that proCANP translocates to the membrane in the presence of microM Ca2+ and is activated at the membrane. The CANP inhibitor and Ca2+ are the most important factors for the regulation of CANP activity. The primary translation product of the mRNA for rabbit liver CANP inhibitor contains four internal repeats. Structural analyses of the liver and erythrocyte inhibitors reveal that they contain four and three repeats, respectively. The repeating unit was identified as the functional unit of the inhibitor and each unit inhibits one mole of CANP. On the basis of these results, an activation mechanism for proCANP at the membrane was proposed. The native enzyme, which has been called CANP or calpain, should now be called proCANP or calpainogen. CANP and calpain should be used for the autolyzed active form.

Animals↗

Codon preference is but an illusion created by the construction principle of coding sequences.

Modern coding sequences are in the periodicto-chaotic transition. In the case of two related sequences for lens alpha A-crystallin and small heat shock protein, the original repeating units were heptameric in length. Accordingly, base trimers that were parts of heptameric units recurred far more frequently than those that were not included. In the crystallin coding sequence, CTG trimer recurred 21 times, and TCT and TCC trimers recurred 17 times each. By contrast, CTA and TCG, although related to the above, recurred only 4 and 3 times, respectively. It is a small wonder that 10 of the 16 leucine residues were encoded by CTG, whereas none was encoded by CTA, and that 17 of the 23 serine residues were encoded either by TCT or by TCC, whereas only 1 was encoded by TCG. In the small heat shock protein coding sequence, however, AGC became parts of the two prominent heptameric recurring units. Not surprisingly, 10 of the 22 serine residues were now encoded by AGC. In conclusion, the so-called codon preference is a mere reflection of the construction principle of coding sequences and has very little to do with selection per se.

Amino Acid Sequence↗

Universal rule for coding sequence construction: TA/CG deficiency-TG/CT excess.

Each coding sequence is a finite resource as to the number and composition of four bases. Accordingly, the excessive recurrence of one base oligomer entails the noticeable underrepresentation by the other, so that if the former is the same in most, if not all, of the coding sequences, the latter too must necessarily be the same in all. Indeed, a previous series of studies on 20-odd divergent coding sequences established CTG as one of the most frequently recurring base trimers (if not the most frequent), and this excess was compensated by the underrepresentation by CG and TA dimer-containing base trimers. In this study, I have analyzed three additional coding sequences and reanalyzed one previously studied coding sequence. These four, derived from man, a plant, and a fish, were of variously lopsided base compositions that were not at all conducive to high recurrences of either CT dimer or CT and TG. Yet, the excess of CT and TG dimers accompanied by complementary deficiency of CG and TA dimers emerged as the common rule. Thus, I propose the above as the universal rule of coding sequence construction. The underrepresentation by CG and TA dimers within coding sequences explains why regulatory signals in intergenic spacers are of two kinds: one, TA dimer rich; and the other, CG dimer rich.

Adenine↗