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Biomedical subjects

H Hamada

Publications and source records attributed to H Hamada.

At least 163 records · Page 9Linked to original sources

Gene therapy for murine renal cell carcinoma using genetically engineered tumor cells to secrete interleukin-12.

To determine the possibility of gene therapy for renal cell carcinoma (RCC) using interleukin-12 (IL-12), we prepared genetically engineered murine RCC cells (Renca) which secrete IL-12 and evaluated the usefulness of these cells as a tumor vaccine. The IL-12 gene was transduced using MFG retroviral vector. The in vitro characteristics of transfectants--i.e., cell proliferation and expression of surface antigens--were then examined. In vivo tumorigenicity was assessed by subcutaneously injecting each type of cell in syngenic BALB/c mice. For the challenge experiments, the mice rejecting previously injected Renca IL-12 cells were rechallenged with parental cells. To determine the antitumor effect at remote sites, mice were injected with parental cells into the left flank, and then either Renca IL-12 or parental cells were inoculated into the opposite site on day 0 or 1. The transfected cells can secrete 146.7 ng/ml/10(6)cells/48 hr of IL-12, as confirmed here by bioassay. The in vitro characteristics of the transfectants were not altered, but in vivo tumorigenicity was significantly reduced. Of the 21 mice that rejected Renca IL-12 cells, 9 failed to develop tumors after the challenge with parental cells. In the mice treated with Renca IL-12 as a vaccine, both number and tumor volume of the mice that developed tumors at remote sites were reduced. IL-12 secreting Renca cells conferred both protective immunity to parental cells and delay of tumor growth at remote sites, indicating that IL-12 secreting Renca cells are a feasible candidate for use in gene therapy of RCC.

Animals↗

Anti-tumor effect of murine renal cell carcinoma cells genetically modified to express B7-1 combined with cytokine secreting fibroblasts.

Recently, many experiments have shown that the expression of the costimulatory molecule B7-1 on tumor cells can induce tumor-specific immunity. These results suggest that tumor cells modified to express costimulatory molecules can be used as a potential tumor vaccine. For this purpose, we transduced B7-1 gene into renal adenocarcinoma cells of spontaneous origin (Renca) in BALB/c mouse using the retroviral vector system. Our results indicated that approximately 60% of cells expressed B7-1 gene product using the retroviral vector system, and that B7-1 transduction did not affect the expression of MHC molecules on tumor cells nor the in vitro growth rate of tumor cells, but only in vivo tumorigenicity. As for the antitumor effect on the remote site, there were no significant differences among parental Renca, Renca lac Z and Renca B7-1 sublines, although tumors grew a little more slowly in the mice injected with Renca B7-1 cells as a vaccine. Even if the growth of tumors was significantly delayed in the mice treated by Renca B7-1 as a vaccine combined with the injection of BALB/c3T3 IL-12 near to the tumor on the same or following day, no significant antitumor effects were observed when the Renca B7-1 cells were injected as a vaccine compared with cytokines near the vaccine site. These results indicated that B7-1 gene transduction can decrease the tumorigenicity of murine renal cell carcinoma cells, but fails to induce sufficient antitumor response when it is used as a tumor vaccine. It is necessary to develop immunogenicity, by such means as irradiation or a combination of appropriate cytokines, to stimulate effective tumor immunity in a therapeutic setting.

3T3 Cells↗

Enzyme/prodrug gene therapy for human colon cancer cells using adenovirus-mediated transfer of the Escherichia coli cytosine deaminase gene driven by a CAG promoter associated with 5-fluorocytosine administration.

Escherichia coli cytosine deaminase (CD), which is a prokaryotic enzyme, converts nontoxic prodrug 5-fluorocytosine (5-FC) into the toxic chemotherapeutic agent 5-fluorouracil (5-FU). To investigate an enzyme/prodrug gene therapy for colorectal cancer, using adenoviral gene transfer of the E. coli CD gene associated with administration of 5-FC, we constructed replication-defective adenovirus vectors expressing the E. coli CD gene or lacZ gene driven by a CAG promoter (composed of a cytomegalovirus immediate early enhancer and a chicken beta-actin promotor). The present study demonstrated that an adenoviral gene transfer system using a CAG promoter induced sufficient gene expression of CD to confer the cytotoxicity of 5-FC to HT29 human colon cancer cells by converting it into 5-FU even at an moi of one. Furthermore, experimental gene therapy using intratumoral injection of the CD-expressing adenovirus with systemical administration of 5'-FC successfully suppressed the growth of established HT29 subcutaneous tumors in nude mice. These results suggest that enzyme/prodrug gene therapy using the adenoviral gene transfer of the E. coli CD gene with concomitant administration of 5-FC may be an effective strategy in the local control of colorectal cancer.

Adenoviridae↗

[Efficacy of stress management classes at a health center].

Although interest in mental health promotion has recently been increasing, the most appropriate approaches remain to be determined. Therefore we conducted Stress Management Classes (SMCs) at Higashi Osaka City Naka Health Center in an attempt to help residents to improve their mental health. The purpose of this study was to evaluate the efficacy of SMCs, held four times over 2 months, with an educational program including the concept of stress and instruction in autogenic training as a relaxation technique. Subjects who attended a Health Promotion Class (HPC) at Osaka Prefectural Kaizuka Health Center were used as controls for the study. The aim of the HPC was to prevent chronic physical diseases such as hypertension, diabetes, and hyperlipidemia, with the program consisting mainly of exercise once a week for 3 months. The results were as follows: 1) People who attended SMCs were more likely to have mental health problems than those who attended the HPC. As a result, mentally ill patients could be diagnosed and receive psychiatric treatment at an early stage in the SMC group. 2) Both SMC and HPC attenders reported improvement of their mental health status with the use of POMS (Profile of Mood States). 3) Both SMC and HPC attenders exhibited significant decrease of blood pressure. Although attenders of both classes improved their mental health status, it is important to be able to attract individuals who are in a poor mental condition in case of mental health promotion. In this trial, we found that the term "stress management" was very useful because people who suffered stress were likely to be interested in it. After the Community Health Law was established in 1994, the flow of community health activities has been shifting from the prefectural government to the municipality. However, promoting mental health and welfare is still mainly the role of the prefectural government. In this sense, health centers are appropriate institutions to hold classes as in this trial.

Autogenic Training↗

Ampullectomy of carcinoma of the papilla of vater in an elderly patient without jaundice.

A 79 year-old woman was admitted to Aioi City Hospital for a closer examination of hepatic dysfunction. A filling defect was observed at the distal end of the intrapancreatic common bile duct by computed tomography combined with drip infusion cholangiography. The diagnosis of adenoma with dysplasia at the papilla of Vater was obtained by a biopsy performed during duodenoscopy. As a result, we performed an ampullectomy. Histologic examination revealed a papillary adenocarcinoma which partly extended just beyond the muscle of Oddi. The patient made an uneventful recovery and was discharged on the 35th postoperative day. Here, based upon our experience, we discuss such problems as the accuracy of preoperative diagnosis and the indications for ampullectomy.

Adenocarcinoma, Papillary↗

[Three cases in which CR was obtained in residual metastatic lesions by intrahepatic arterial infusion after resection of hepatic metastases from colorectal carcinoma].

We report three cases in which CR was maintained after infusion (WHF) was performed for residual metastatic lesions following resection of hepatic metastases from colorectal cancer. (Case 1) A 55-year-old female with sigmoidal cancer and hepatic metastases, H2 (4 lesions). Right lobectomy and partial resection of the left lobe were performed. On the third month following surgery, CT showed two lesions in the lateral segment of the left lobe, and WHF was then begun. One month after the start of infusion, the lesions calcified and following that, disappeared. Infusion was performed for 12 months and the total amount of 5-FU was 52.8 g. Eight years and nine months following surgery, the patient is currently alive and without recurrence. (Case 2) A 65-year-old male with rectal cancer and hepatic metastases, H3 (6 lesions). Four lesions were removed by hepatic resection; however, 2 deep lesions in S4 and S5 were left unresected. WHF was begun one month following surgery, following which the lesions were undetectable by either CT or US. Infusion was performed for 18 months and the total amount of 5-FU was 81 g. Two years and ten months after surgery an isolated lung metastasis was discovered in the right lung and a thoracoscopic partial resection was performed. Eight years and four months following the original surgery and five years and four months following the lung operation the patient is alive and without recurrence. (Case 3) A 55-year-old male with rectal cancer and subsequently discovered hepatic metastases, H3 (5 lesions). Resection of the lateral segment and a partial resection of the right lobe were performed; however, one deep lesion in S7 was left unresected. WHF was begun on the 10th day following surgery. At about eight months there was a change in shape and shrinkage of the lesion. Infusion was performed for 11 months and the total amount of 5-FU was 48 g. Ten months following surgery, CT showed a new lesion in S7 and a partial resection was performed. Intraoperative US confirmed the disappearance of the previous residual lesion in S7. One year and one month following the original surgery, the patient is alive and without recurrence. From these results, it is suggested that with postoperative WHF it is possible to obtain a complete cure in cases of colorectal cancer with hepatic metastases without the resection of all lesions. (*WHF: 5-FU 1,000 mg/m2/5 hrs/week).

Aged↗

High level calcineurin activity predisposes neuronal cells to apoptosis.

Calcineurin is a Ca(2+)/calmodulin-dependent protein phosphatase that is abundantly expressed in several specific areas of the brain, which are exceptionally vulnerable to stroke, epilepsy, and neurodegenerative diseases. In this study, we assessed the effects of high level activity of calcineurin on neuronal cells. Virus-mediated high level constitutive activity of calcineurin rendered neuronal cells susceptible to apoptosis induced by serum reduction or by a brief exposure to calcium ionophore. Adenovirus-mediated, high level forced activity of calcineurin induced cytochrome c/caspase-3-dependent apoptosis in neurons. Preincubation with the calcineurin inhibitors cyclosporin A and FK506 reduced susceptibility to apoptosis. High level constitutive expression of Bcl-2 or CrmA or incubation with a specific caspase-3 inhibitor inhibited the calcineurin-induced apoptosis. These data indicate that high level constitutive activity of calcineurin predisposes neuronal cells to cytochrome c/caspase-3 dependent apoptosis even under sublethal conditions.

Adenoviruses, Human↗

Adenovirus-mediated transfer of p33ING1 with p53 drastically augments apoptosis in gliomas.

The p53 tumor suppressor gene is an important target for the gene therapy of cancers, and clinical trials targeting this gene have been conducted. Some cancers, however, are refractory to p53 gene therapy. Therefore, it has been combined with other therapies, including chemotherapy and radiotherapy, to enhance the cytopathic effect of p53 induction. The p33ING1 gene cooperates with p53 to block cell proliferation. In this study, we investigated whether adenovirus (Adv)-mediated coinduction of p33ING1 and p53 enhances apoptosis in glioma cells (U251 and U-373 MG), which showed no genetic alterations but low expression levels of p33ING1. Although the single infection of Adv for p33ING1 (Adv-p33) at a multiplicity of infection (MOI) of 100, or Adv for p53 controlled by myelin basic protein (MBP) promoter (Adv-MBP-p53), a glioma-specific promoter, at a MOI of 50, did not induce apoptosis in U251 and U-373 MG glioma cells; coinfection of Adv-p33 and Adv-MBP-p53 at the same MOIs induced drastically enhanced apoptosis in both cell lines. Apoptosis was not induced in NGF-treated PC-12 cells infected with a high MOI (300) of Adv-p33 nor in those coinfected with Adv-p33 (100) and Adv-MBP-p53 (50). Coinfection of Adv-p33 and Adv-MBP-p53 demonstrated morphological mitochondrial damage during the initial stage of apoptosis, which likely led to apoptotic cell death. Our results indicate that this coinfection approach can be used as a modality for the gene therapy of gliomas, sparing damage to normal tissues.

Adenoviridae↗

Relative level of expression of Bax and Bcl-XL determines the cellular fate of apoptosis/necrosis induced by the overexpression of Bax.

The Bax protein plays a critical role in the apoptosis of cancers induced by radiotherapy or chemotherapy, which induce both apoptosis and necrosis. We transduced various glioblastoma cells with the Bax gene via an adenoviral vector and found that A-172 cells led to necrotic cell death, while U251 cells apoptotic cell death, even though a similar level of Bax protein was introduced. A-172 cells displayed a much higher constitutive expression of the Bcl-XL protein compared with that of U251 cells. Upon simultaneous overexpression of the Bcl-XL and Bax proteins in the U251 cells, Bax-induced apoptosis of U251 cells was suppressed and an increase in the number of necrotic cells was seen. Moreover, induction of a higher amount of Bax protein in A-172 cells increased the percentage of apoptotic cells. In conclusion, if a cancerous cell expresses a high enough amount of Bax to undergo death, apoptosis will be induced. If a cancerous cell expresses a level of Bcl-XL which prevents Bax-induced apoptosis, the overexpression of Bax leads to necrotic cell death.

Apoptosis↗

Expression level of Bcl-2 determines anti- or proapoptotic function.

Bcl-2 is an oncogene with antiapoptotic function. However, Bcl-2 is converted to a Bax-like death effector by caspases, suggesting that the expression of Bcl-2 may not favor the growth of cancers. We introduced the Bcl-2 gene to gliomas via adenovirus (Adv; Adv-Bcl-2) with the Adv for Fas (Adv-Fas) and the Adv for Fas ligand (Adv-FL) to evaluate the antiapoptotic function of Bcl-2. In U251 glioblastoma cells, Bcl-2 at a low level of expression repressed apoptosis induced by Adv-Fas and Adv-FL, whereas Bcl-2 at a high level of expression did not. On the other hand, Bcl-X(L) showed antiapoptotic function against Fas-mediated apoptosis, irrespective of its expression level. In glioblastoma cells, induction of Bcl-2 alone at a high level induced apoptosis, whereas induction of Bcl-X(L) alone did not. As the multiplicity of infection of Adv-Bcl-2 was increased, the quantity of a cleaved product of Bcl-2 increased. Induction of caspase-inhibitory genes (CrmA and p35) inhibited apoptosis induced by Adv-Bcl-2. Induction of Bcl-2 led to alteration of the membrane potential and structure of the mitochondria. In summary, although Bcl-2 at a low level of expression was antiapoptotic, Bcl-2 at a high level of expression was proapoptotic to Fas-mediated apoptosis. Overexpression of Bcl-X(L) was consistently antiapoptotic to Fas-mediated apoptosis.

Apoptosis↗

Adenovirus-mediated gene transfer of Bcl-xL prevents cell death in primary neuronal culture of the rat.

Bcl-xL is a Bcl-2-related gene that regulates programmed cell death in a bcl-2-independent fashion. It is expressed in tissues containing long-surviving postmitotic cells, such as neurons in adult brains. To investigate the possibility of gene therapy for transferring this anti-apoptotic gene into the neuron for the treatment of vascular occlusive or neurodegenerative diseases, we examined the effect of a replication-deficient recombinant adenovirus vector coding human Bcl-xL gene on the augmentation of the survival of primarily-cultured rat neuronal cells in vitro. Immunoblot analysis revealed that primarily-cultured neuronal cells were successfully infected and transferred with this gene by recombinant adenovirus vector with high transduction efficiency. Bcl-xL gene transfer to the primarily-cultured neurons could prevent these cells from cell death.

Adenoviridae↗

Ion chromatography of nitrite at the ppb level with photometric measurement of iodine formed by post-column reaction of nitrite with iodide.

The difficulty in ion-chromatographic determination of nitrite in aqueous solutions containing a high concentration of chloride arises mainly from incomplete resolution of the peaks for these anions on the separation column whose efficiency is not high. A photometric measurement of iodine formed by a reaction of nitrite with iodide has been found to make it possible to determine, chromatographically, trace amounts of nitrite without any interference from chloride; chloride does not oxidize iodide to produce iodine. The proposed method was based on the separation of nitrite from matrix anions on a silica-based anion-exchange column with a 1.5.10(-3) M phthalate eluent (pH 5.0), followed by photometric measurement of the iodine (as triiodide) formed via a post-column reaction of the separated nitrite with iodide. The optimal conditions for the post-column reaction were established by varying the concentrations of iodide, copper(II) and nitric acid in a post-column-reaction solution and the length of a reaction tube. A calibration graph for nitrite, plotted as peak heights versus concentrations, was linear up to 1.50.10(-5) M (690 ppb). The detection limit, defined at S/N = 3, was 1.00.10(-7) M (4.60 ppb) nitrite. The presence of chloride ions up to 0.01 M did not give any interference to the determination of nitrite. This method was successfully applied to the determination of nitrite in lake water, river water, sewage works water and snow samples without any pretreatment.

Chromatography, Ion Exchange↗

Highly augmented cytopathic effect of a fiber-mutant E1B-defective adenovirus for gene therapy of gliomas.

An E1B 55-kDa gene-defective adenovirus (Adv), ONYX-015, has been reported to be a highly useful replication-competent Adv that shows cytopathic effect for cancers with an abnormal p53 gene, without damaging normal tissues. In this study, we combined this Adv (Adv-E1AdB) with a fiber mutation, F/K20, which has a stretch of 20 lysine residues added at the COOH-terminus of the fiber and shows high transduction efficiency to gliomas. In U-373 MG glioma cells, the transduction efficiency of Adv-F/ K20 for lacZ was nine times higher than that of the Adv with wild-type fiber (Adv-F/wt) for lacZ. At a multiplicity of infection of 30, the replication efficiency of Adv-E1AdB-F/K20 was 11 times higher than that of Adv-E1AdB with wt fiber (Adv-E1AdB-F/wt). The ED50 value of AdvE1AdB-F/K20 to U-373 MG cells, which is a measure of the in vitro cytopathic effect, was 32 times greater than that of Adv-E1AdB-F/wt. injection of Adv-E1AdB-F/K20 suppressed the in vivo growth of tumors. The antitumoral effect of Adv-E1AdB-F/K20 was remarkably stronger than that of Adv-E1AdB-F/wt. A greater quantity of replicated virus protein (hexon) by infection with Adv-E1AdB-F/K20 was demonstrated in vitro and in vivo, compared with that of Adv-E1AdB-F/wt. In conclusion, gene therapy using Adv-E1AdB-F/K20, which drastically augmented the antitumoral effect of Adv-E1AdB, will be a promising therapeutic approach for gliomas.

Adenovirus E1B Proteins↗

Determination of left/right asymmetric expression of nodal by a left side-specific enhancer with sequence similarity to a lefty-2 enhancer.

The nodal gene is expressed on the left side of developing mouse embryos and is implicated in left/right (L-R) axis formation. The transcriptional regulatory regions of nodal have now been investigated by transgenic analysis. A node-specific enhancer was detected in the upstream region (-9.5 to -8.7 kb) of the gene. Intron 1 was also shown to contain a left side-specific enhancer (ASE) that was able to direct transgene expression in the lateral plate mesoderm and prospective floor plate on the left side. A 3. 5-kb region of nodal that contained ASE responded to mutations in iv, inv, and lefty-1, all genes that act upstream of nodal. The same 3. 5- kb region also directed expression in the epiblast and visceral endoderm at earlier stages of development. Characterization of deletion constructs delineated ASE to a 340-bp region that was both essential and sufficient for asymmetric expression of nodal. Several sequence motifs were found to be conserved between the nodal ASE and the lefty-2 ASE, some of which appeared to be essential for nodal ASE activity. These results suggest that similar transcriptional mechanisms underlie the asymmetric expression of nodal and of lefty-2 as well as the earlier expression of nodal in the epiblast and endoderm.

Animals↗

Activated dendritic cells from bone marrow cells of mice receiving cytokine-expressing tumor cells are associated with the enhanced survival of mice bearing syngeneic tumors.

Dendritic cells (DCs), which phagocytose antigens and subsequently proliferate and migrate, may be the most powerful antigen-presenting cells that activate naive T cells. To determine their role in the immune response to tumors, we used WEHI-3B murine leukemia cells transduced with adenovirus vectors expressing cytokines. We found that mixtures of irradiated cells expressing granulocyte-macrophage colony-stimulating factor (GM-CSF) plus those expressing interleukin-4 (IL-4) or tumor necrosis factor alpha (TNFalpha) protected mice against WEHI-3B-induced leukemias. When bone marrow mononuclear cells (BMMNCs) obtained from mice that had been injected with irradiated, cytokine-expressing tumor cells were injected into tumor-bearing mice, the survival of the latter was significantly prolonged; the longest survival was observed in mice receiving BMMNCs containing an increased number of DCs from animals injected with a mixture of tumor cells expressing GM-CSF with those expressing IL-4. Assay for antileukemic effects in spleen of the latter animals showed specific antitumor cytotoxicity against WEHI-3B, suggesting that DCs from donor mice activate specific T cells in the tumor-bearing recipients. These results suggest that the infusion of syngeneic BMMNCs stimulated with cytokine-expressing tumor cells may be effective in treating certain types of tumors.

Adenoviridae↗

Enhanced therapeutic efficacy of tumor RNA-pulsed dendritic cells after genetic modification with lymphotactin.

Pulsing dendritic cells (DCs) with tumor cell-derived mRNA is regarded as an attractive alternative in the development of DC-based tumor vaccines. Our aim is to improve the therapeutic efficacy of DC-based tumor RNA vaccines by augmenting the preferential chemotaxis of DCs to T cells. Mouse bone marrow-derived DCs were genetically modified with lymphotactin (Lptn) by adenovirus vector, which conferred on DCs preferential chemotaxis to CD4+ and CD8+ T cells (Cao et al., 1998). Lptn gene-modified DCs (Lptn-DCs) were pulsed with tumor mRNA and used for vaccination in the tumor models of 3LL lung carcinoma and B16 melanoma. In both tumor models, immunization with 4 X 10(4) tumor RNA-pulsed Lptn-DCs induced more potent CTL activity, compared with their counterparts, specifically against tumor cells and Mut1 or tyrosinase-related protein 2 (TRP-2) peptide-pulsed RMA-S cells, and rendered the immunized mice resistant to tumor challenge much more effectively. CD8+ T cells were necessary and sufficient to generate the protection of Lptn-DC-based RNA tumor vaccines, and CD4+ T cells were required for the induction of tumor rejection. In the preestablished 3LL and B16 tumor models, vaccination with DC-based or LacZ-DC-based tumor RNA vaccines (2 X 10(5) cells) could reduce pulmonary metastasis and extend survival of tumor-bearing mice, but was less effective than the Lptn-DC counterpart (with 60-80% mice surviving). When the immunizing dose was decreased to 4 X 10(4) cells, Lptn-DC-based tumor vaccines rather than their counterparts were still significantly effective. Our studies provide a potential strategy to improve the efficacy of DC-based vaccines, and a new approach to immunological intervention by chemokines.

Adenoviridae↗

Successful adoptive immunotherapy of murine poorly immunogenic tumor with specific effector cells generated from gene-modified tumor-primed lymph node cells.

We previously reported that cytokine gene transfer into weakly immunogenic tumor cells could enhance the generation of precursor cells of tumor-reactive T cells and subsequently augment antitumor efficacy of adoptive immunotherapy. We investigated whether such potent antitumor effector T cells could be generated from mice bearing poorly immunogenic tumors. In contrast to similarly modified weakly immunogenic tumors, MCA102 cells, which are chemically induced poorly immunogenic fibrosarcoma cells transfected with cDNA for IL-2, IL-4, IL-6, IFN-gamma, failed to augment the host immune reaction. Because priming of antitumor effector T cells in vivo requires two important signals provided by tumor-associated Ags and costimulatory molecules, these tumor cells were cotransfected with a B7-1 cDNA. Transfection of both IFN-gamma and B7-1 (MCA102/B7-1/IFN-gamma) resulted in regression of s.c. tumors, while tumor transfected with other combinations of cytokine and B7-1 showed progressive growth. Cotransfection of IFN-gamma and B7-1 into other poorly immunogenic tumor B16 and LLC cells also resulted in the regression of s.c. tumors. Cells derived from lymph nodes draining MCA102/B7-1/IFN-gamma tumors showed potent antitumor efficacy, eradicating established pulmonary metastases, but this effect was not seen with parental tumors. This mechanism of enhanced antitumor efficacy was further investigated, and T cells with down-regulated L-selectin expression, which constituted all the in vivo antitumor reactivity, were significantly increased in lymph nodes draining MCA102/B7-1/IFN-gamma tumors. These T cells developed into potent antitumor effector cells after in vitro activation with anti-CD3/IL-2. The strategy presented here may provide a basis for developing potent immunotherapy for human cancers.

Animals↗

Monitoring of mercury pollution in Tanzania: relation between head hair mercury and health.

Through 1996 into 1997, a spot investigation on mercury contamination was conducted three times in Tanzania, especially around the Lake Victoria. A total of 150 goldminers, 103 fishermen and their families, and 19 residents of Mwanza City volunteered for the current study. A high total mercury level of 48.3 ppm (near to 50 ppm, a critical level of Minamata disease) and over in the head hair was observed in six goldminers (highest value, 953 ppm), four fishermen and their families (highest value, 416 ppm), and four Mwanza people (highest value, 474 ppm). With the exception of these 14 subjects, however, each mean total mercury level was well within the normal range (below 10 ppm). Out of the goldminers examined, 14 cases were diagnosed as a mild form of inorganic-mercury poisoning according to their clinical symptoms (such as polyneuropathy mercurialis, neuroasthemia, or tremor mercurialis) and the low ratio of methylmercury to total mercury, whereas neither inorganic-mercury poisoning nor methylmercury poisoning (Minamata disease) was noted in the fishermen and their families or in the Mwanza people. In addition, some subjects who showed a high total mercury level made habitual use of toilet soap containing much mercury. The findings obtained suggest that the mercury pollution in Tanzania is not very serious, however, it should be observed continuously.

Adolescent↗