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Biomedical subjects

J Hanai

Publications and source records attributed to J Hanai.

At least 37 records · Page 2Linked to original sources

International cooperation in neonatal screening: technical training course for newborn and infant screening.

We report the outline and results of our experience with a group training course of neonatal screening for health care professionals in developing countries. Sapporo City Institute of Public Health (SCIPH) has been offered a training course on neonatal screening once a year since 1991 under the Technical Training Program of the Japan International Cooperation Agency (JICA). The aims of this training course are to enhance the participants' technical knowledge and skills, and also to deepen their understanding of the principle of neonatal screening as well as the relevant diseases. Lectures and laboratory practice on phenylketonuria (PKU), congenital hypothyroidism (CH), congenital adrenal hyperplasia (CAH) and neuroblastoma are included in the 3-month program. After the completion of the training, participants are expected to play a major role in establishing and expanding neonatal screening system in each of their countries. We have received a total of 67 participants from 25 countries until March 1998: 58 pediatricians; 2 gynecologists; 6 biochemists; 1 administrative officer. After they returned to their countries, 11 engaged in neonatal screening and started PKU and CH screening in their institute, city or province in Argentina, Brazil, Mexico, Peru and Thailand. We believe that these results fulfilled our objectives. Also, for follow-up, SCIPH has been giving information and consultation to the participants on requests. This international cooperation network could also benefit our present network of the International Society Screening in the future.

Developing Countries↗

Mass screening for neuroblastoma targeting children age 14 months in Sapporo City: a preliminary report.

BACKGROUND: In Sapporo City a mass screening program for neuroblastoma targeting children age 6 months (6-MS) was initially introduced in 1981. Since April 1991, an additional program has been implemented, aimed at children age 14 months (14-MS). METHODS: High performance liquid chromatography was employed in the 14-MS. Identification of cases was dependent on the Registry of Childhood Malignancies in the Hokkaido Prefecture. RESULTS: Of the 85,783 live births in Sapporo City during the period 1990-1994, a total of 56,444 participated in the 14-MS (compliance rate, 65.8%). By the end of 1996, of 48,448 children who had previously taken part in the 6-MS, 6 cases were identified in the 14-MS, and 1 additional case screened negative but was later diagnosed clinically. Two more cases were detected in the 14-MS among the 7996 children who had not participated in the 6-MS. Though the incidence of cases identified by the 14-MS was much higher than expected, several true-positive cases had unfavorable histology (as defined by Shimada's classification), a high dopamine level, and/or a high homovanillic acid/vanillylmandelic acid ratio. CONCLUSIONS: Mass screening of children age 14 months for neuroblastoma detects cases missed or unscreened at age 6 months, though the detection rate appears to be in excess of what would be expected from natural incidence.

Cross-Sectional Studies↗

Peanut lectin-binding sites and mucins in benign and malignant colorectal tissues associated with schistomatosis.

An immunohistochemical and histochemical comparative study was carried out in benign and malignant colorectal tissues with and without schistosomiasis. This included a quantitative determination of peanut lectin (PNA)-binding sites and proliferating cell nuclear antigen (PCNA) expression and histochemical detection of mucin changes. 133 cases were studied, including 70 cases of colorectal carcinoma associated with schistosomiasis (CCS) and 63 cases of colorectal carcinoma without schistosomiasis (CC). Significant differences were found in the type of mucin-containing carcinomas (MC) between CCS and CC. 65% of non-tumorous mucosa adjacent to MC of the CCS group expressed PNA-binding sites, significantly higher than those of the MC in the CC group (31%). The non-tumorous mucosa in cases of MC of the CCS group also showed a high percentage of sialomucin-predominant secretion (69%, vs 38% in MC of the CC group). Consistently, the presence of PNA-binding sites in MC tumors of the CCS group was increased, compared with that in the same subtype in the CC group (respectively 65% and 31% of strong positivity for PNA). However, no differences in expression of PNA and mucin changes were demonstrated in the surrounding mucosa and tumorous tissues of non-mucin-containing carcinomas (NMC) between CCS and CC. The expression of PCNA was not different between CCS and CC and their subtypes. Our findings suggest a close relationship between mucin-containing colorectal carcinomas and schistosomiasis japonica.

Colorectal Neoplasms↗

Smad6 inhibits signalling by the TGF-beta superfamily.

SMAD proteins have been identified as signalling mediators of the TGF-beta superfamily, which is involved in a range of biological activities including cell growth, morphogenesis, development and immune responses. Smad1, Smad2, Smad3 and Smad5 are ligand-specific: Smadl and Smad5 transduce signals from bone morphogenetic proteins, and Smad2 and Smad3 mediate signalling by TGF-beta and activin, whereas Smad4 acts as a common signalling component. For example, Smad2 is phosphorylated by the TGF-beta type I receptor upon ligand binding, forms a heteromer with Smad4, and then translocates into the nucleus where it activates transcription. Here we report the isolation of Smad6 in the mouse. Smad6 is quite different in structure from the other SMAD proteins, and forms stable associations with type I receptors. Smad6 interferes with the phosphorylation of Smad2 and the subsequent heteromerization with Smad4, but does not inhibit the activity of Smad3. Smad6 also inhibits the phosphorylation of Smad1 that is induced by the bone morphogenetic protein type IB receptor. These data indicate that signals of the TGF-beta superfamily are regulated both positively and negatively by members of the SMAD family.

Amino Acid Sequence↗

TGF-beta receptor-mediated signalling through Smad2, Smad3 and Smad4.

Smad family members are newly identified essential intracellular signalling components of the transforming growth factor-beta (TGF-beta) superfamily. Smad2 and Smad3 are structurally highly similar and mediate TGF-beta signals. Smad4 is distantly related to Smads 2 and 3, and forms a heteromeric complex with Smad2 after TGF-beta or activin stimulation. Here we show that Smad2 and Smad3 interacted with the kinase-deficient TGF-beta type I receptor (TbetaR)-I after it was phosphorylated by TbetaR-II kinase. TGF-beta1 induced phosphorylation of Smad2 and Smad3 in Mv1Lu mink lung epithelial cells. Smad4 was found to be constitutively phosphorylated in Mv1Lu cells, the phosphorylation level remaining unchanged upon TGF-beta1 stimulation. Similar results were obtained using HSC4 cells, which are also growth-inhibited by TGF-beta. Smads 2 and 3 interacted with Smad4 after TbetaR activation in transfected COS cells. In addition, we observed TbetaR-activation-dependent interaction between Smad2 and Smad3. Smads 2, 3 and 4 accumulated in the nucleus upon TGF-beta1 treatment in Mv1Lu cells, and showed a synergistic effect in a transcriptional reporter assay using the TGF-beta-inducible plasminogen activator inhibitor-1 promoter. Dominant-negative Smad3 inhibited the transcriptional synergistic response by Smad2 and Smad4. These data suggest that TGF-beta induces heteromeric complexes of Smads 2, 3 and 4, and their concomitant translocation to the nucleus, which is required for efficient TGF-beta signal transduction.

Activin Receptors, Type I↗

Mass screening for neuroblastoma and mortality in birth cohorts.

Mortality resulting from neuroblastoma in birth cohorts in both Sapporo City and the whole of Japan was investigated to evaluate the effects of a high-performance liquid chromatography (HPLC) mass screening program, targeting on 6 month-old infants. In Sapporo City, the non-HPLC screened cohort showed no reduction in mortality at 4 years of age compared with the pre-screening cohort. However, the HPLC screened cohort showed a reduction of 69% in mortality compared with the pre-screening cohort. On a nation-wide scale, there was a significant decline in mortality for the non-HPLC screened cohort compared with the pre-screening cohort; for the HPLC screened cohort for 1989-1991, there was also a reduction in mortality for children younger than 2 years of age. The incidence of neuroblastoma at 1-4 years of age in the HPLC cohort in Sapporo City was about half that in the pre-screening cohort, along with and probably because of an increasing incidence among infants in the same cohort. Our findings suggest that HPLC screening may detect some poor-prognosis neuroblastoma cases at early stages, thus providing for more favorable therapy.

Adolescent↗

Mass-screening of neuroblastoma using urine from infants by high-performance liquid chromatographic method: results of first (6th month) and second (14th month) screening.

To detect neuroblastoma in early stages, mass-screening of this tumor was carried out by HPLC method using the urine of six-month-old infants. Screening began in April, 1981, and a total of 42 cases were detected by December, 1994. The incidence of detection was about 1:5,000 babies tested. All of these patients have survived without relapses except one, who died of surgical complications. Nevertheless, tumors developed at later stages in 14 cases from the group which resulted negative at the 6-month screening. To determine whether such tumors could be detected by a second check, a 14-month screening was carried out, beginning in April, 1991. By December, 1994, 3 patients with neuroblastoma were found among 41,809 babies tested, and were subsequently treated. While one of these three patients was not screened at 6 months, the other two had shown approximate cut-off values in urinary VMA as well as HVA at their 6-month screening. Therefore, if the tumors had already existed at the 6-month screening, and had grown gradually until the second check at 14 months, at least some of these tumors were of the late-onset variety and could have been detected at an earlier stage.

Chromatography, High Pressure Liquid↗

[A case of malignant hemangioendothelioma of the lung with rapid growth of pulmonary metastasis].

Malignant hemangioendothelioma of the lung is very rare and difficult to diagnose. The growth is rapid and the prognosis is very unfavorable. We report an operated case of the disease with rapid growth of pulmonary metastasis. The silver, vimentin and factor VIII stainings were available for diagnosis of this disease. The 46-year-old female patient died of bleeding from the pulmonary metastasis eight months after the operation without other distant metastasis. Even if a lung tumor is pointed out and thought to be benign, frequent follow up is necessary. Furthermore, we recommend positive lung biopsy by thoracotomy or video-assisted-thoracic-surgery.

Female↗

Failure to detect dopaminergic neuroblastoma in a mass-screening system.

Dopaminergic neuroblastoma comprised 12% of the patients under 1 year of age, and 83% of the older ones. Seven cases were missed by the mass-screening system performed at age 6 months and were detected after 16 months. Three of these advanced cases were positive only for dopamine. These findings supports our second mass-screening system using dopamine evaluation at age 14 months.

Age Factors↗

Myeloperoxidase-antineutrophil cytoplasmic antibody-positive crescentic glomerulonephritis complicating the course of Graves' disease: report of three adult cases.

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis has been recently recognized in Graves' disease patients treated with propylthiouracil. We have experienced three adult cases of Graves' disease with main features being renal derangements. All three patients, who were between the ages of 22 and 82 years, had been treated with propylthiouracil for 2 to 5 years after a diagnosis of Graves' disease. After several weeks of upper respiratory tract infection or flu-like symptoms, they abruptly began to manifest proteinuria and hematuria concomitant with severe anemia. Their serum creatinine increased from normal levels to 1.2 to 3.6 mg/dL. Renal biopsy revealed crescentic glomerulonephritis without deposition of immune complexes (ie, pauci-immune type). Crescent formations were observed in 40% to 60% of the glomeruli in all three cases. The serum from the patients revealed positive perinuclear-ANCA and negative cytoplasmic-ANCA (C-ANCA) pattern, and myeloperoxidase (MPO)-ANCA titers were 120 to 502 ELISA Units/mL (normal, < 10 ELISA Units/mL). A withdrawal of propylthiouracil with or without immunosuppressive therapy ameliorated their renal derangements. Graves' disease patients should be placed under vigilant observation by monitoring their urinalysis and serum creatinine, especially when being treated with antithyroid drugs and when suffering from flu-like symptoms.

Adult↗

Differences in colorectal cancer between China and Japan: a clinical and histological study of two groups of cases.

It is well known that most tumours are attributed to life style, especially the tumours of the digestive system. Clinical and histopathological investigation of tumours in different human groups and societies, and analysis of the variations will provide evidence for this, and is one of the approaches to study carcinogens. Clinical data obtained from 391 patients with colorectal cancer at the Sakai Municipal Hospital, Japan, and Shanghai Jinshan Hospital and Cancer Hospital, China, from 1987 to 1992, included the sex, age and tumour subsite. Sections of histological specimens were also retrieved. The results were compared between two countries. The average age of patients with colorectal cancer in Shanghai was 8.5 years less than in the Sakai group. The age peak of the former was 51-60, and in the latter, 61-70 years. The most frequent site of the cancer in the Shanghai group was the rectum, contrasting with the higher percentage of sigmoid colon cancer in Sakai group. There was also a significant difference in histological subtype of the cancer between the two groups. Mucinous adenocarcinoma was notably more common in the Shanghai group than in the Sakai group, and the high frequency was mainly in the colon. All of the variations were suggested to be attributable to differing socioeconomic circumstances and lifestyle, especially the dietary habits of the countries.

Adult↗

A trial to discriminate spontaneous regression from non-regression cases during mass screening for neuroblastoma.

We tried to discriminate between cases of spontaneous regression and non-regression during mass screening for neuroblastoma, taking advantage of differences in respect to the urinary homoranillic acid/vanillyl mandelic acid (HVA/VMA) ratio and the original tumor site among true positive, false negative and natural occurrence cases. After classifying them into a total of six groups depending on the two factors, ratio: < 1, 1-2 or > or = 2 and tumor site: adrenal or extra-adrenal in origin, we calculated the mathematical probability of a given true positive case being one of spontaneous regression. A tumor of extra-adrenal origin was likely to regress spontaneously, especially one with an HVA/VMA ratio < 1 or > or = 2 (82.2-100%). A tumor of adrenal origin with an HVA/VMA ratio < 1 seemed unlikely to regress spontaneously (0-4%). The present method, employing simple preoperative information, would be useful in future for the selection of true positive cases which should be observed without treatment.

Adrenal Gland Neoplasms↗

[Two cases of metastatic lung tumor from leiomyosarcoma of the uterus].

Three pulmonary resections were performed for two cases of metastatic lung tumor from uterine leiomyosarcoma. Case 1 was diagnosed as myoma uteri. Preoperative chest X-ray examination showed an abnormal shadow in the left upper lobe. Postoperative diagnosis was leiomyosarcoma. During radiotherapy for the pelvic lesion, the lung tumor was growing very rapidly and micrometastases were detected bilaterally without distant metastasis. Bilateral pulmonary resections were performed. Three months and 15 days later, second left pulmonary and thoracic wall resections were performed because of lung and pleural recurrence. Seven months after the first pulmonary operation, she died of systemic metastases. Case 2 was admitted to the hospital because of genital bleeding and diagnosed leiomyosarcoma of the uterus. The patient had a metastatic lung tumor in the left lower lobe preoperatively. Eighteen days after hysterectomy, left lower lobectomy was performed because progressive hemoptysis occurred for rapidly enlarged metastatic lesion. She died of intrapelvic bleeding three months after the operation without respiratory symptom. The prognosis of synchronously found out lung metastasis from uterine leiomyosarcoma is very poor. Neither chemotherapy nor radiotherapy is effective. Although it's difficult and controversial to decide the surgical indication, we need to operate on as soon as possible when there is no other distant metastasis. Even if the timing of operation is late, we can find the surgical significance of pulmonary resection for reduction of respiratory symptoms and probability of longer survival.

Female↗

[Relationship between tissue concentrations of 5-FU and degeneration of tissues after UFT administration in patients with bladder tumor].

The relationship between the 5-FU concentration and tissue degeneration was studied in the bladder tumor tissue after UFT administration. In 12 patients with bladder tumor, UFT 400 mg/day was administered orally for about 2 weeks before TUR, and tegaful, 5-FU and uracil concentrations were examined in the blood and the tumor tissue taken about 6 hours after the last administration. Tumor tissue was also taken before and after the UFT administration, and the degree of cell degeneration due to UFT administration were evaluated by light and electron microscopy. The 5-FU concentration was significantly higher in the tumor tissue (0.078 +/- 0.091 microgram/g) than in the serum (0.017 +/- 0.010 microgram/ml). Signs of degeneration were observed in tumor cells after UFT administration in all 6 patients in whom the tumor tissue 5-FU concentration was 0.046 microgram/g or higher. Mitosis was not increased after UFT administration in any of the 12 patients.

Aged↗

[Myelodysplastic syndrome developing acute myelocytic leukemia with gastric mucormycosis].

80-year-old female was admitted to our hospital because of pancytopenia. Her peripheral and bone marrow examinations were performed. According to the criteria of FAB classification, the diagnosis was myelodysplastic syndrome (refractory anemia with excess of blasts in transformation). Etoposide was administered to decrease leukemic blasts. However, she still had high fever and increasing of CRP. Hematological data also showed the increasing of WBC count, blast cells, and LDH enzyme. Antibiotics and anti fungal drugs were also not effective. She died of respiratory failure, although the cautions and extensive treatment was tried. Autopsy findings revealed proliferation of mucor in the mucosa of stomach. So, we reported here a very rare case of gastric mucormycosis, localizing exclusively in the stomach which was difficult to diagnose while she was alive.

Aged↗

Expression of intermediate filaments and other special markers by testicular germ cell tumors. With reference to embryogenesis.

Distribution of intermediate filament proteins (IFs) and several special markers was studied in 39 testicular germ cell tumors and 8 embryos and foetuses. The similarity and difference between development of germ cell tumor and embryogenesis were immunohistochemically investigated. Seminoma and embryonal carcinoma, as tumoral counterparts of undifferentiated germ cells, were characterized by little IF expression. This study revealed that the maturing and differentiating process in germ cell tumor is different from normal embryonal development and the tumor cells showed leaping maturing steps in tumorigenesis. Immunostaining for IFs helped to discover the further differentiation occurring in embryonal carcinoma and to demonstrate heterogeneous elements in non-seminoma germ cell tumors, which sometimes might not be apparent by light microscopical observation of H&E staining section. According to the findings, two patterns in mixed germ cell tumors are suggested; i.e., combined and diffuse types. The mechanism of tumorigenesis of the two types is supposed to be different. Clinically, the prognosis of most patients with testicular germ cell tumor is fairly good because of the improved chemotherapies that are dependent on histological diagnosis.

Adolescent↗

Mass screening of neuroblastoma in Sapporo City, Japan.

In Sapporo City a mass screening program for neuroblastoma aiming at 6-month-old infants has been performed since April 1981. By March 1990, 136,001 infants were screened; 26 true-positive cases of neuroblastoma and six false-negative cases were detected. The sensitivity of the mass screening method was about 80% throughout the 9 years. During the 9-year period, a total of nine children with neuroblastoma who were not screened were also identified. Clinical stage, age at diagnosis, and survival rate for the 32 patients who were screened (26 true positives and six false negatives) were much more favorable than those for the nine patients who were not screened. A remarkable decrease in the incidence of cases of neuroblastoma with advanced clinical stages over 1 year of age, especially among children 1-4 years of age, was noted after the start of the mass screening. The mortality from this tumor in children up to 4 years of age significantly decreased after the start of the urinary screening program. Rescreening at 14 months of age was begun in April, 1991 in Sapporo City. Performing two screening examinations decreases the probability of overlooking a patient. Thus, it is expected that tumors missed on the first screening would be detected by the second screening.

Biomarkers, Tumor↗