Search PubMed⌕ Search

Biomedical subjects

T Harada

Publications and source records attributed to T Harada.

At least 289 records · Page 16Linked to original sources

Recurrent T354P mutation of the Na+/I- symporter in patients with iodide transport defect.

Iodide transport defect (ITD) is a rare disorder causing congenital hypothyroidism. We previously reported that homozygous T354P mutation in the sodium/iodide symporter (NIS) gene caused ITD. To clarify the prevalence of this mutation, artificial substitution introducing PCR followed by restriction enzyme analysis was developed as a rapid screening method to detect the T354P mutation. Three apparently unrelated families with ITD, one patient with low thyroidal 99mTc pertechnetate (99mTcO4-) uptake and 52 healthy controls (104 alleles) were analyzed for this mutation. All families with ITD harbored the mutation, suggesting that T354P is a recurrent mutation and a major cause of ITD. This was not a widespread mutation, because it was not detected in the 52 unrelated normal controls. Because two cases with homozygous T354P mutation developed multinodular goiters within their second decade of life though they had been maintained in euthyroid state, homozygous T354P mutation alone and/or low intrathyroidal iodide and high serum TSH level in early life might account for tumorigenesis. The patient with low thyroidal 99mTcO4- uptake did not harbor the T354P mutation. Because familial hypocalciuric hypercalcemia was also present in this family, a possibility of the combined abnormality of TSH receptor and calcium functions, which includes an abnormality around the G protein, may be examined further.

Carrier Proteins↗

Genetic mapping of RAPD markers linked to the densonucleosis refractoriness gene, nsd-1, in the silkworm, Bombyx mori.

In the silkworm, Bombyx mori, nonsusceptibility to B. mori densonucleosis virus type-1 (BmDNV-1) is controlled by a recessive gene, nsd-1 (nonsusceptibility to DNV-1), located on the twenty-first chromosome. We investigated genetic linkage between five random amplified polymorphic DNA (RAPD) markers and the +nsd-1 gene. Initially, we constructed the CSD-1 strain (nsd-1/+) which is congenic to strain C137 (nsd-1/nsd-1) for the twenty-first chromosome, starting with a female of C137 and a male of strain J137 (+nsd-1/+nsd-1). For the crossing over experiment, a female of C137 was crossed with a male (nsd-1/+) of CSD-1. Segregation analysis showed that the most closely linked RAPD marker mapped 3.0 cM distant from +nsd-1. A more specific marker for +nsd-1 was made by converting this RAPD band into a sequence characterized amplified region (SCAR) using a series of newly designed primer pairs based on its DNA sequence.

Animals↗

Hypophosphatemic rickets accompanying congenital microvillous atrophy.

This report concerns an 11-year-old boy who manifested hypophosphatemic rickets associated with congenital microvillous atrophy (CMA). He had been suffering from vomiting and severe diarrhea from the first day of life and had been treated with total parenteral nutrition (TPN) since he was 67 days old. At 4 years of age, intestinal biopsy resulted in a diagnosis of CMA. He was admitted to our hospital complaining of leg pain at the age of 11. Laboratory data revealed hypophosphatemia, elevated serum 1, 25-dihydroxyvitamin D (1,25(OH)2D) levels, and hypercalciuria. A roentgenogram showed rickets in the extremities. A balance study of phosphate in urine and stool indicated that the amount of phosphate leaking into the stool was greater than that into the urine. Moreover, the total amount of phosphate leaking from both the intestine and kidney exceeded the amount of phosphate intake from TPN. The rickets was healed by increasing the phosphate concentration in TPN. This case is different from X-linked hypophosphatemic rickets but similar to hereditary hypophosphatemic rickets with hypercalciuria (HHRH) in terms of hypercalciuria and elevated serum 1,25(OH)2D levels. The effectiveness of phosphate treatments used here is also similar to that used for HHRH. However, this type of hypophosphatemic rickets is unique in that phosphate leaking into the intestine plays an important role in its pathogenesis.

Absorptiometry, Photon↗

Morphological variations in transplanted tumors developed by inoculation of spontaneous mesothelioma cell lines derived from F344 rats.

Morphological and immunohistochemical features of the abdominal mesotheliomas that were developed by inoculation of 3 cell lines (MeET-4, -5 and -6) established from spontaneous abdominal mesotheliomas in male F344 rats. Although the original tumors of three cell lines showed signs of epithelioid growth with a predominantly simple papillary pattern, transplanted tumors revealed a variety of morphologic features including epithelioid with glandular structures, sarcomatous, and a mixture of these components. All tumor cells of transplanted tumors were positive for alpha-smooth muscle actin (ASMA) but almost negative for desmin as were epithelioid cells of the original tumors, and the cell lines were positive for desmin but not for ASMA. These results suggested that mesothelioma in the F344 rat had the potential for wide spectrum differentiation under in vitro conditions. The microenvironmental factors obtained in vivo can modify their potential ability and their morphological aspects. These factors may be related to tumor cell reexpression of ASMA of tumor cells that were masked under in vitro culture conditions.

Abdominal Neoplasms↗

Pulmonary macrophage mobilization in hamsters after cessation of smoking.

Male Syrian hamsters were exposed to smoke from three different types of cigarettes rated as mild, medium, and strong on the basis of their smoke chemistry for 4 weeks. These hamsters were euthanized at 0, 1 and 2 weeks of recovery after the last smoke exposure to study the pulmonary cell response after cessation of smoking. The free macrophage count determined on lung sections stained with hematoxylin and eosin was used as the index to evaluate the rate of recovery from smoke-related insult caused by the different types of cigarettes. The number of macrophages in the smoke-exposed hamsters was consistently greater throughout the recovery period than in the controls, depending on the amount of particulate components including tar and nicotine in the test cigarettes. The macrophage mobilization peaked at the first week of recovery and then showed a tendency to decrease at the second week. At the second week, however, the hamsters exposed to smoke from strong or medium cigarettes still showed significantly higher counts than the controls, while no significant change was noted in those exposed to smoke from mild cigarettes. These results indicate that the process and duration of recovery after cessation of smoking may depend on the extent of particulate matter impinging on the respiratory tract, so that strong cigarettes would be more hazardous because of greater number and longer retention of macrophages in the lung.

Animals↗

Liddle's syndrome in an elderly woman.

A 78-year-old woman with hypertension was hospitalized with acute bronchitis. However, she was also found to have hypernatremia, hypokalemia, and metabolic alkalosis. Detailed examination showed a low plasma renin activity and plasma aldosterone concentration. A provisional diagnosis of Liddle's syndrome was established and the patient was successfully treated with triamterene. Although Liddle's syndrome is generally considered an inherited hypertensive disease found in young people, a review of the literature indicated that muscle weakness is an important clinical finding in elderly patients with this disease. Liddle's syndrome should be considered in the differential diagnosis of hypertension even in elderly individuals.

Aged↗

[Two cases of tinea capitis with different clinical courses].

We report cases of two 4-year-old boys with tinea capitis who attend the same daynursery. Clinically, on the first visit both lesions were a superficial type, however we initiated treatment with a dose of 50 mg/day of oral itraconazole. Althougth the lesion of case 2 improved after 11 weeks of treatment, case 1 developed to kerion celsi and required continued treatment for 22 weeks for cure. Microsporum canis was isolated from the hairs of both cases and MIC of itraconazole against both isolates was 1 micro g/ml. We specurate that secondary bacterial infection was responsible for the development to kelion celsi in case 2.

Antifungal Agents↗

[Is a maxillary prosthesis difficult for patients with trismus?].

Of patients with a postoperative maxillary defect, around 30% are though to have trismus to some extent. In these patients, some difficulty in fabricating a maxillary prosthesis is expected. In this study, 54 patients with trismus were compared with a control group to find some proof of difficulty in making a maxillary prosthetics. Fifty-four of trismus less than 20 mm of a mandibular stroke were experienced out of 185 patients with maxillary prosthetics between October 1984 and October 1992. The trismus was divided into 4 groups of less than 5 mm (1 case), 5 mm-10 mm (10 cases), 11 mm-15 mm (19 cases), and 16 mm-20 mm (24 cases). These case were analyzed by in taking an impression failure, average weight of the prosthesis, time needed to complete the prosthesis and some special form of prosthesis. No apparent differences among the 4 groups or with the control group were found. The cause of the difficulty in making a prosthesis for such patients with trismus are suggested not to be simply due to the range of mouth opening but also to the complexed space formed by the dental defect, alveolar bone defect, spreadability of the lip and the cheek, the mandibular stroke and the so-called scar bundle of the cheek next to the defect.

Adult↗

[An autopsy case of sudden death caused by untreated sepsis after complete remission of acute promyelocytic leukemia].

The patient was 63 year-old man. He had been diagnosed as acute promyelocytic leukemia (APL) and treated until 4 month before his death with complete remission. The patient suddenly died 9 days after he complained of occipital headache. Autopsy and histopathologic findings were as follows: the left pleura was thick and calcificated with abscess, compatible with the findings of old tuberculosis complicated with bacterial infection. Furthermore, polynuclear leukocytes and gram-positive micro-organisms were accumulated in the lungs, and pyogenic meningitis, pyonephritis, splenitis were also found. Bacteologically, Streptococcus pneumoniae was detected from cadaver's blood and cerebrospinal fluid. Therefore, we concluded that the patient was died of septic shock caused by systemic infection of Streptococcus pneumoniae. The mortality of septic shock is high and in some patients, causative organisms may not be isolated. In the present case, although the original inflammation was left pleuritis due to Streptococcus pneumoniae, correct clinical diagnosis was not made before death as the patient had lacked any complaints except for occipital headache. This case revealed that the cause of sudden death was sepsis induced by Streptococcus pneumoniae instead of a relapse of APL. This case also illustrated the importance of reviewing the previous history of a patient and doing postmortem bacteologic examination in a case of suspected sepsis.

Cause of Death↗

[Autoantibody to glutamate decarboxylase in a patient with spinocerebellar degeneration and Sjögren syndrome].

We report a 52-year-old woman with Sjögren syndrome from the age of 46, developed cerebellar ataxia, autonomic dysfunction and dysarthria at 50. She had no family history, and all known causes of cerebellar disease were excluded. Serum of the patient contained autoantibodies directed against glutamic acid decarboxylase (GAD) which was an enzyme involved in the biosynthesis of GABA. She also had autoantibodies that were specific with Sjögren syndrome (SS-A, anti-nuclear antibody). Anti-GAD antibody changed into negative after high dose intravenous and oral corticosteroid therapy, but symptoms did not improve. Western blot method revealed abnormal bands to human neuroblastoma cell line (10, 43, 49 kDa), considered relatively specific to nervous tissue. In this case cerebellar ataxia and atrophy were caused by autoimmune pathogenesis including cerebellar GABAergic system and central nerve cells.

Autoantibodies↗

Ocular tilt reaction with vertical eye movement palsy caused by localized unilateral midbrain lesion.

A 60-year-old man developed diplopia and experienced difficulty moving his eyes. Vertical movement of each eye, including vestibulo-ocular reflex and smooth pursuit, was extremely limited. Horizontal eye movements were normal. His head position was tilted toward his left. There was 10 prism diopters of exotropia and 10 prism diopters of right hypertropia. Fundus photographs revealed a clockwise torsion of both eyes. These signs indicate leftward ocular tilt reaction. Magnetic resonance imaging showed a small area of an increased signal intensity localized in the midbrain dorsomedial to the red nucleus on the right side. Based on recent experimental evidence, it may be assumed that the unilateral lesion involving the right interstitial nucleus of Cajal most probably caused leftward ocular tilt reaction in our patient.

Cerebral Hemorrhage↗

Treatment of hepatoblastoma: less extensive hepatectomy after effective preoperative chemotherapy with cisplatin and adriamycin.

BACKGROUND: Although the prognosis of hepatoblastoma was improved by the introduction of cisplatin and doxorubicin (Adriamycin) for adjuvant chemotherapy, extensive hepatectomy continues to be the usual practice. We retrospectively reviewed our recent experience with hepatoblastoma to determine whether the new modality of intensive chemotherapy could change the resectability, extent of hepatectomy, operative complications, and prognosis. METHODS: The clinical features of 15 children with hepatoblastoma treated between 1985 and 1995 were reviewed. Intensive chemotherapy was added before surgical resection not only when a tumor was unresectable but also when it was large enough to increase the risk of operative morbidity. RESULTS: There was 100% resectability, and the overall mortality rate was only 6.7%. Fourteen patients have been free of disease for 2 to 12 years. Preoperative chemotherapy enabled resection of six previously unresectable hepatoblastomas. Moreover, hepatic resection tended to be less invasive in several patients whose tumors had been much reduced after preoperative chemotherapy. Intraoperative and postoperative complications were minimal, with a short operative time and small amount of blood loss, especially in the group with delayed primary operation. CONCLUSIONS: The preoperative administration of cisplatin and Adriamycin reduced the tumor size so that a safe hepatectomy could be performed with less blood loss and minimal technical complications. Unnecessary sacrifice of the normal hepatic tissue was avoided by performing the less extensive hepatectomy.

Antineoplastic Combined Chemotherapy Protocols↗

[A case manifested overlapping neuropathologic features of both progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD)].

A 62-year-old man developed clumsiness, vertical ophthalmoplegia, right-side dominant parkinsonism, pyramidal signs, limb-kinetic apraxia and dementia. His brain MRI and SPECT revealed mild fronto-parietal atrophy and hypoperfusion predominately on the right side. At the age of 65, the patient died of sepsis. The duration of his illness was approximately 3 years. Clinical diagnosis was corticobasal degeneration (CBD). On neuropathological examination, there was no neuronal loss and many neurofibrillary tangles (NFTs) in the cerebral cortices. Basal ganglia and substantia nigra showed moderate to severe neuronal loss. And there were many NFTs and argyrophillic threads (threads) in the subthalamic nucleus and nuclei of the brainstem. These findings were almost compatible to those of PSP. However, the following findings were atypical for PSP, 1) mild atrophy and absence of gliosis in the tegmentum of the brain stem, 2) Mild neuronal loss in the subthalamic nucleus and the dentate nucleus without grumose degeneration. Furthermore, characteristic findings were noted on modified Gallyas-Braak stain. Numerous threads and many astrocytic plaques (AP) were shown in cerebral cortices, which were particular to CBD cases. So this case demonstrated neuropathological findings of both PSP and CBD. Therefore, it was difficult to classify this case as either PSP or CBD, and we diagnosed this case as a neuropathological overlapping case of both PSP and CBD.

Aged↗

[Three adults with mild varicella and bronchial mucosal lesions].

We encountered three adults with varicella and bronchial mucosal lesions. Respiratory symptoms were minimal in all three. Chest X-ray films showed bilateral, diffuse, small, nodular shadows. Small, elevated lesions with white plaque's were seen on the bronchial mucosa bronchoscopically. Transbronchial lung biopsy, bronchial mucosal biopsy, and bronchoalveolar lavage were also done. The lung-biopsy specimen showed infiltration of lymphocytes into the interstitial space: VZV antigen was found by immunohistochemical staining of the lesion in one case. Analysis of bronchoalveolar lavage fluid revealed abnormally low CD 4/8 ratios in three cases. These findings suggest a high incidence of respiratory complications, especially bronchial lesions, despite the lack of respiratory symptoms, in adults with varicella.

Adult↗

[A case of impending neuroleptic malignant syndrome associated with Shy-Drager syndrome].

We report a 55-year-old man with impending neuroleptic malignant syndrome who showed a remarkable dysautonomia such as dysuria and was treated with L-dopa under the diagnosis of Shy-Drager syndrome. The patient demonstrated fever, leukocytosis and elevated serum creatine kinase by a decrease in L-dopa dose. Probably, he developed impending neuroleptic malignant syndrome, induced by urinary tract infection as well as decrease in L-dopa dose. Since Shy-Drager syndrome is often treated with antiparkinsonian drugs, neuroleptic malignant syndrome can possibly develop after the change in dosage of catecholaminergic drugs. The imbalance of neurotransmitters and receptors in the central autonomic nervous system may participate in the development of neuroleptic malignant syndrome. Accordingly, Shy-Drager syndrome can easily be associated with neuroleptic malignant syndrome because of its severe disturbance in the autonomic nervous system. However, autonomic nervous dysfunction, a major sign of neuroleptic malignant syndrome, might be masked by symptoms of Shy-Drager syndrome. Therefore, diagnosis of neuroleptic malignant syndrome is often delayed. Careful observations of patients with Shy-Drager syndrome related with an antiparkinsonian drug are necessary, especially when the dose of drugs is changed or the general condition deteriorates.

Antiparkinson Agents↗

Potent inactivator of alpha-chymotrypsin: 2,2-dimethyl-3-(N-4-cyanobenzoyl)amino-5-phenyl pentanoic anhydride.

We synthesized a novel potent alpha-chymotrypsin inactivator, 2,2-dimethyl-3-(N-4-cyanobenzoyl) amino-5-phenyl pentanoic anhydride, which fulfilled the criteria of a mechanism-based inactivator: first-order kinetics, irreversibility, saturation kinetics and substrate protection. The inactivation rate constant (kinact) and the enzyme-inhibitor dissociation constant (KI) were calculated to be 0.017s-1 and 0.071 microM, respectively (kinact/KI = 242,000 M-1s-1). These kinetic parameters indicate that this compound is one of the most powerful alpha-chymotrypsin inactivators ever reported. The average number of alpha-chymotrypsin turnovers per inactivation (partition ratio) was calculated to be 1, which indicates that it is a stoichiometrically ideal inactivator of alpha-chymotrypsin. We compared the IC50 values of this compound with those of several chymotrypsin-like serine proteinases (bovine alpha-chymotrypsin, recombinant human chymase and human neutrophil cathepsin G) and a metallo proteinase, rabbit angiotensin converting enzyme (ACE). Our compound, 2,2-dimethyl-3-(N-4-cyanobenzoyl) amino-5-phenyl pentanoic anhydride, inhibited bovine alpha-chymotrypsin potently (IC50 = 1.0 (+/- 0.2) x 10(-9) M) as well as other chymotrypsin-like serine proteinase; recombinant human chymase (IC50 = 7.0 (+/- 1.0) x 10(-8) M) and human neutrophil cathepsin G (IC50 = 1.8 (+/- 0.2) x 10(-7) M). However, rabbit ACE was not inhibited by this compound (IC50 > 1 x 10(-4) M).

Anhydrides↗