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Biomedical subjects

K Yamashiro

Publications and source records attributed to K Yamashiro.

At least 73 records · Page 4Linked to original sources

Molecular cloning of a novel trypsin-like serine protease (neurosin) preferentially expressed in brain.

A cDNA encoding a precursor for a novel serine protease (neurosin) was cloned from a cDNA library prepared from a human colon adenocarcinoma cell line, COLO 201. The sequence consisted of 155 bp 5' non-coding region and a 732 bp open reading frame which was followed by a 551 bp 3' non-coding region. The predicted protein consists of 244 amino acids which is possibly processed to an active enzyme of 223 amino acids that shows some similarity (< 30%) to other members of serine protease family. As found in other trypsin-like proteases, the enzyme contains the catalytic triad which is characterized as the essential amino acid residues for the activity. Northern blot analyses of the mRNA showed the strongest expression in brain followed by a lower but significant one in spleen. A construct of cDNA encoding chimeric protein that carries pro-sequence of trypsin II and putative mature neurosin starting from Leu22 was transfected to COS-1 cells. Successful production of the active neurosin was shown after treating the supernatant of the culture of the transfectants with enterokinase.

Adenocarcinoma↗

Results of 1001 pancreatic resections for invasive ductal adenocarcinoma of the pancreas.

OBJECTIVE: To evaluate the recent results of pancreatic resection in patients with invasive ductal adenocarcinoma of the pancreas. DESIGN: Retrospective study. SETTING: Seventy-seven medical facilities belonging to the Japan Society of Pancreatic Surgery. PATIENTS: One thousand one patients who underwent a resection of the pancreas between January, 1, 1991, and December 31, 1994. MAIN OUTCOME MEASURES: Morbidity and survival after surgery for pancreatic cancer according to the modified TNM classification of the International Union Against Cancer. RESULTS: After pancreatic resection, the cumulative postoperative survival rates at 1 and 3 years were 44.5% and 10.3%, respectively. Patients with early-stage cancers had a more prolonged survival time, ie, the cumulative 3-year survival rates for patients with stage I or stage II cancers were 50.4% and 45.5%, respectively; the survival rates for patients with stage III and stage IVa and IVb cancers were 17.6%, 5.7%, and 0%, respectively. The survival rate for patients with N1 or N2 metastasis did not differ appreciably, and both groups had significantly better survival rates than patients with N3 metastasis (P < .001). A significant difference in the postoperative survival time of N1 metastasis was observed between patients with no lymph node dissection (mean survival, 326.4 days) and patients who received a lymph node dissection (D1) (mean survival, 478.2 days) (P < or = .01). CONCLUSIONS: The recent results of pancreatic resection for invasive ductal adenocarcinoma of the pancreas are generally unsatisfactory. Although the outcome of the patients with an N1 metastasis can be improved if they receive N1 lymph node dissection (D1), an extensive lymph node dissection in advanced cancers does not necessarily produce a favorable prognosis.

Adult↗

Establishment of a new continuous clear cell sarcoma cell line. Morphological and cytogenetic characterization and detection of chimaeric EWS/ATF-1 transcripts.

Clear cell sarcoma (CCS), a rare tumour of deep soft tissues, often has a t(12; 22) (q13; q12) translocation that induces the formation of a hybrid EWS/ATF-1 gene. To investigate these alterations further, we established a new continuous cell line directly from a CCS taken from a 9-year-old girl. The cultures were characterized with respect to morphological, ultrastructural, immunohistochemical and karyotypical features and were tested by reverse transcription PCR (RT-PCR) for chimaeric EWS/ATF-1 transcripts. The continuous cell line, designated KAO, is tumorigenic in nude mice, and the resultant tumours resemble the primary CCS. The tumour cells and the cultured cells have melanosomes in their cytoplasm and are immunoreactive with the melanoma-specific antibody HMB45, but do not express S-100 protein. The cultured CCS cells have the t(12; 22)(q13; q12) translocation and express the hybrid EWS/ATF-1 gene. No transcripts of the hybrid gene were detected in a malignant cutaneous melanoma tested simultaneously. Although CCS and malignant melanoma are morphologically related, the present results suggest that their geneses differ at the chromosome and molecular levels. They also indicate that chromosome analysis and detection of fusion EWS/ATF-1 transcripts may be useful adjuvant tools for the diagnosis of CCS.

Activating Transcription Factor 1↗

Demonstration of fragments with thyroid stimulating activity from thyroid stimulation blocking antibodies-IgG molecules by papain digestion.

OBJECTIVES: Thyroid stimulation blocking antibodies (TSBAb) inhibit TSH action and may have a role in the pathogenesis of hypothyroidism. In order to study the relationship between blocking and stimulating activities we have examined the biologically active fragments in TSBAb-IgG molecules after papain digestion. DESIGN: Both thyroid stimulating (TS) activity (cAMP production in thyroid cells) and TSH binding inhibitory (TBI) activity (determined by TSH receptor assay) in sera from patients with primary hypothyroidism were examined after digestion with papain-Sepharose in the presence of cysteine. The digested IgG was separated into unbound (UF) and bound (BF) fractions on a Protein A-Sepharose column. Each fraction was then gel-filtrated on a Sephadex G-100 column. RESULTS: TS activity was found within one hour after hydrolysis in 5 out of 7 antibodies, then gradually decreased after more prolonged incubation. Both TS and TBI activities in the UF and the BF from Protein A were found in Feb (Mr 50 kD) and the second protein peak (Fc with trace amounts of Fab), respectively. The biological activity in the second protein peak was suggested as being derived from Fab fraction, because the activity bound to the anti-F(ab')2 column. However, the first peak (undigested IgG) in the BF had neither TS nor TSB activity. The TS activity in the retarded fraction (less than Mr 20 kD) in the UF gradually increased with prolonged digestion. CONCLUSIONS: The conversion of Thyroid stimulation blocking antibodies activity to thyroid stimulating activity by papain digestion suggests that the inherent thyroid stimulating activity located in the Fab portion of the IgG molecule is unmasked by papain cleavage. We also suggest that the thyroid stimulating activity in the retarded fraction in the unbound fraction may be released from hydrolysis of the Fab portion of the IgG molecule.

Antibodies, Blocking↗

Purification and characterization of neutral alpha-mannosidase from hen oviduct: studies on the activation mechanism of Co2+.

Neutral alpha-mannosidase was purified to homogeneity from hen oviduct. The molecular mass of the enzyme was 480 kDa on gel filtration, and the 110-kDa band on SDS-PAGE in the presence of 2-mercaptoethanol indicated that it is composed of four subunits. The activated enzyme hydrolyzed both p-nitrophenyl alpha-D-mannoside and high mannose-type sugar chains. This substrate specificity is almost the same as that reported for the neutral a-mannosidase from Japanese quail oviduct [Oku and Hase (1991) J. Biochem. 110, 982-989]. Manalpha1-6(Manalpha1-3)Manalpha1-6(Manalpha1-3) Manbeta1-4GlcNAc (Km =0.44 mM) was hydrolyzed four times faster than Manalpha1-6(Manalpha1-3)Manalpha1-6(Manalpha1-3) Manbeta1-4GIcNAcbeta1-4GlcNAc, and Manalpha1-6(Manalpha1-2Manalpha1-2Manalpha1-3)++ +Manbeta1-4GlcNAc was obtained as the end product from Man9GlcNAc on digestion with the activated alpha-mannosidase. The enzyme was activated 24-fold on preincubation with Co2+. The activation with other metal ions, like Mn2+, Ca2+, Fe2+, Fe3+, and Sr2+, was less than 5-fold, and Zn2+, Cu2+, and Hg2+ inhibited the enzyme activity. The optimum pHs for both the enzyme activity and activation with Co2+ were around 7. The cobalt ion contents of the purified, EDTA-treated, and Co2+-activated enzymes were 1.5, 0.0, and 3.9, respectively, per molecule. Since the Co2+-activated enzyme gradually lost its activity on incubation with EDTA and the activity was restored promptly on the addition of Co2+, the binding of Co2+ to the enzyme seems to be essential for its activation. The results obtained with protease inhibitors together with those of the SDS-PAGE before and after activation, showed that the proteolytic cleavage reported for the activation of monkey brain alpha-mannosidase seems not to be involved.

Animals↗

Characteristics of neurons with high-frequency discharge in the central nervous system and their relationship to chronic pain. Experimental and clinical investigations.

High-frequency extracellular unitary activity was recorded mainly in the ventral caudal nucleus of the thalamus in chronic-pain patients. These high-frequency discharge (hyperactive) neurons shows three types of discharge pattern with different interval histograms. Some of these hyperactive neurons were suppressed by the administration of a calcium antagonist (nicardipine). In an experimental study, chronic-pain models were made in rats according to the method of Lombard et al. (1979). From these animals, hyperactive neurons were recorded from the contralateral thalamic nuclei, lemniscus medialis. Hyperactive neurons were examined via electrical stimulation of and/or iontophoretic application. The results suggest that there is some relationship to the glutamatergic and GABAergic (probably GABAA) fibers or receptors.

Animals↗

[Histopathological examinations of dural arteriovenous malformations of posterior fossa].

Two cases of dural arteriovenous malformation (DAVM) of the posterior fossa were presented and a histopathological examination was described. After embolization of the feeding arteries, DAVMs of the posterior fossa were removed with the adjacent sinus. Serial sections of the surgical specimens showed an abnormal mass with dilated, tortuous vessels of varying diameters in the sinus wall, and partially hyalinized connective tissue around the vessels. The elastic lamina of the sinus wall was interrupted and a mass of abnormal vessels developed into the subintimal layer of the sinus. Fistulas, about 200 microns in diameter, were formed between arterialized dural veins and dural arteries which had obvious internal elastic lamina. An opening of the fistula of the abnormal vessel, 25 microns in diameter, to the sinus lumen was also seen. No stage of organized thrombus could be seen in the sinus lumen. These findings strongly suggested that physiologically existing arteriovenous fistulas within the dura mater, which have been reported by Kerber et al, had developed due to many factors which increase intracranial pressure. They protruded into the sinus lumen in such a way that it could cause stenosis or obstruction of the sinus. In conclusion it can be said that an obstructive lesion of dural sinus is considered of itself to be DAVM in most cases and sinus thrombosis is the result of the DAVM.

Adult↗

[Transarterial platinum coil embolization for direct carotid-cavernous fistula].

Two cases of direct carotid-cavernous fistula (CCF) were treated by transarterial platinum coil embolization (TACE) following unsuccessful transarterial balloon embolization (TABE). Case 1 was a 47-year-old man who complained of pulsatile left exophthalmos, chemosis and bruit. Left carotid angiograms showed a CCF with anterior, posterior and cortical venous drainage. Near total obliteration of the CCF was achieved by TABE, but it showed recurrence in the next morning. At this time, left carotid angiograms showed a CCF which drained only into the cortical veins via the enlarged sphenoparietal sinus. Because of high risk of intracranial hemorrhage, TACE was performed immediately. The result was successful. Case 2 was an 82-year-old woman who suffered from traumatic subarachnoid hemorrhage. First right carotid angiograms showed a small CCF which drained only into the inferior petrosal sinus. Right exophthalmos, swelling of the eyelids, severe eye pain and bruit appeared gradually. The second right CAG performed three months after the head trauma showed markedly dilated superior ophthalmic vein which was the new main draining root of the CCF. Because of progressive symptoms, TACE was performed immediately after the angiography, which proved successful. Direct CCFs must be treated aggressively because they don't cure by spontaneous obstruction of fistula. Although TABE is the first choice for direct CCF, complete occlusion of CCF in difficult in some cases. Those cases have; 1) small fistula of CCF for balloon insertion, 2) large fistula for occlusion by balloons, 3) not enough space for inserting a balloon after recurrence of CCF, and 4) sharp objects (bone fracture fragments, foreign objects) may puncture the balloon. If TABE couldn't provide successful treatments, TACE should be considered as an alternative treatment for direct CCF after angiography without delay because it is less complex compared with TABE.

Aged↗

Intravascular lymphomatosis diagnosed by transbronchial lung biopsy.

Intravascular lymphomatosis is a rare lymphoma presenting a variety of symptoms due to proliferation of tumour cells within blood vessels in the brain, the skin and other organs. This disease is generally considered to be highly malignant, but to be relatively susceptible to combined chemotherapy, when diagnosed in the early stage. We describe a case of intravascular lymphomatosis, presenting with diffuse interstitial shadows on chest radiographic image, which could be diagnosed by transbronchial lung biopsy. The patient showed a good response to combined chemotherapy. We propose that transbronchial lung biopsy is a useful procedure for the diagnosis of intravascular lymphomatosis.

Antineoplastic Combined Chemotherapy Protocols↗

[Combination chemotherapy of continuous infusion 5-fluorouracil and daily low-dose cisplatin in advanced gastrointestinal and lung adenocarcinoma].

Continuous intravenous infusion (c.v.i.) of 5-fluorouracil (5-FU) plus daily low-dose cisplatin (CDDP) was evaluated in 45 patients with advanced and recurrent unresected colorectal, lung, gastric and pancreatic adenocarcinoma. 5-FU was given at a dose of 320 mg/m2/day, c.v.i. for 4 weeks, and CDDP between 3.5 to 7 mg/m2/day, infused for one hour five times a week for 4 weeks. Patients received 1 to 3 cycles of treatment (average 1.5 cycle). Pancreatic cancer cases needed longer treatment periods (2.25 cycles). The response rate of colorectal cancer cases was 57.7% (15/26), pancreas cancer 40%, gastric cancer 62.5%, and lung cancer 66.7%. The overall response rate was 57.8%. No severe side effects occurred in any of these cases. These data indicate that this combination 5-FU + daily low-dose CDDP chemotherapy is effective in the treatment of advanced gastrointestinal and lung adenocarcinoma.

Adenocarcinoma↗

[Tumor marker--present and future].

It is known that the serum in cancer patients has the characteristics of the heat-stability. The factor produce the heat-stability is known to be due to tumor marker(TM) such as CEA, CA125(glycoprotein), CA19-9, CA15-3, SLX, CA50, CA72-4, DU-PAN-2, ST-439, SPAN-1(mucin) and alpha 1-acid glycoprotein, IAP(acute reactants). CEA belongs to IgG supergene family protein and is not oncofetal protein. CA19-9 is synthesis in subjects with Le(a) or Le(b) type, but negative in Le(a- b-) type. Thus, CA19-9 is not available as TM in Le(a- b-) type. Many TMs can be classified in 3 types because cancer cell has the character of immature cells which composed of immature proteins or glycoproteins. (1) Oncofetal protein: AFP(fetal albumin), PTHrP(fetal PTH) (2) The immature isozyme type: increase of amylase(salivary type), CPK(brain type) and aldolase (muscle and brain type) (3) The immature protein in biosynthesis process: increase of precursor protein(prepro type or pro type) such as PIVKA-II(preprothrombin), ProGRP, TPA or CYFRA 21-1(pro-keratin?) and hormone precursor in hormone producing tumor.

Biomarkers, Tumor↗

Beneficial effects of administering intraportal prostaglandin E1 postoperatively to hepatectomy patients with massive intraoperative blood loss.

Massive intraoperative blood loss is a major cause of complications following hepatectomy. To evaluate the efficacy of intraportal prostaglandin E1 (PGE1) for preventing liver deterioration in hepatectomy patients with an intraoperative blood loss of over 2000 ml, a retrospective analysis was conducted on 10 patients given intraportal PGE1 (portal group), 6 given intravenous PGE1 (venous group), and 10 given no treatment (control group). PGE1 was infused at 250 or 500 micrograms/day in the portal group and at 720 micrograms/day in the venous group, and continued for 3 days postoperatively. Alanine aminotransferase (ALT) and total bilirubin (T.Bil) were measured on postoperative days (PODs) 1, 3, 5, and 7. ALT was lower in the portal group than in the other two groups on each POD, and significantly lower than in the control group on POD3 (P < 0.05). T.Bil was significantly lower in the portal group than in the control group on PODs 5 and 7 (P < 0.05). T.Bil on POD 7 was under 1.5 mg/dl in 1 (10.0%), 6 (60.0%), and 2 (33.3%) of the control, portal, and venous group patients, respectively, with a significant difference between the control and portal groups (P < 0.05). These results confirmed that intraportal PGE1 was beneficial for improving hepatic function and preventing cholestasis in patients with a blood loss of over 2000 ml at risk of developing postoperative liver deterioration.

Adult↗

Hyperplastic callus formation in both femurs in osteogenesis imperfecta.

A 3-year-old boy with osteogenesis imperfecta had hyperplastic callus formation in the right femur, without preceding trauma or fracture. Radiologically, this bony mass in the femoral shaft mimicked osteosarcoma. Open biopsy showed that it was benign and suggested hyperplastic callus formation. Seven months after the biopsy, the hyperplastic callus had practically vanished. A similar process developed in the left femur 1 year later, also without fracture.

Bony Callus↗

Kaposi's sarcoma associated with lung cancer and immunosuppression.

We report a 65-year-old Japanese woman with Kaposi's sarcoma (KS). The eruption first occurred on the legs while she was admitted for treatment of poorly differentiated lung cancer. Approximately eight months after the evolution, cutaneous tumors rapidly spread to the forearms, trunk, and pharynx. At that time, the patient had received systemic corticosteroid (10-40 mg/day of prednisolone) for about three months to reduce pulmonary inflammation. The laboratory data showed anemia, lymphopenia, hypogammaglobulinemia, and a decreased T cell count, although the serological test for HIV infection was negative. The patient was treated with radiation (X-ray for KS of pharynx and electron beam for KS of lower legs) and local intralesional injection of vinblastine. Although both therapies were very effective and well tolerated, she died of bacterial pneumonia and sepsis. Autopsy revealed KS tumors, unknown before death, in both lungs, the esophagus, and the stomach. The left lung cancer had disseminated and metastasized to the right lung, pleura, mediastinum, and abdominal cavity. It is suspected that chronic respiratory distress and systemic use of corticosteroids might have induced the rapid extension of KS.

Fatal Outcome↗

Eosinophils negatively regulate eosinophilopoiesis by decreasing IL-5 levels.

The effect of mature eosinophils on eosinophilopoiesis was studied. Mature eosinophils decreased the interleukin-5 (IL-5) level after incubation with IL-5 and suppressed IL-5 release from non-adherent mononuclear cells. These findings suggest that eosinophils negatively regulate eosinophilopoiesis by decreasing the IL-5 level.

Eosinophilia↗

[Percutaneous endoscopic gastrostomy in patients with swallowing difficulties--home care and long-term result].

We studied the possibility of home care of patients who are unable to swallow. Postsurgical complications during the short term (within a week), medium term (within a month) and long term (more than a month) were recorded along with survival time. We also retrospectively studied the number of patients who were discharged after percutaneous endoscopic gastrostomy from November 1989 to March 1995. The percentage of patients with short-term postsurgical complications was 12.1%. Vomiting was the most frequent complication during the medium term and the long term. The weekly rate of complication development (total complications number/total survival time) was highest in the short term and decreased year by year. It was lower in those who were discharged from the hospital than in those who were not discharged. The average survival time was 460.2 days (544.7 days: home care group, 419.0 days: hospital group). The one-year survival rate was 58%, and the two-year survival rate was 36%. One third (32.8%) of patients were cared for at home after gastrostomy (average duration of care at home: 338.5 days) and the average duration of care at home as a percentage of survival time was 58.8%. We conclude that Percutaneous endoscopic gastrostomy can improve the quality of life of patients who are unable to swallow, and may allow them to be cared for at home.

Activities of Daily Living↗

[A successfully operated case of tuberous sclerosis presenting with intractable epilepsy].

A 20-year-old male patient with tuberous sclerosis was admitted to our hospital complaining of intractable epilepsy. He had been suffering from frequent seizures despite anticonvulsant treatment since the age of 1 year. CT scan and magnetic resonance images showed multiple calcified lesions at the paraventricle and temporal lobe on both sides. Electroencephalogram showed left temporal lobe dominant spike waves. After deep electrodes were inserted into the left amygdala and hippocampus and subdural electrodes were placed on the left temporal cortex, clinical seizures were monitored by video and EEG. The primary focus was found in the amygdala. Left temporal lobectomy was carried out through the cranio-orbital zygomatic approach. Postoperatively, the patient has been seizure-free for one year. Despite multiple intracerebral lesions in tuberous sclerosis, resection of the primary epileptogenic focus is needed to solve the seizure problem if the focus is localized.

Adult↗