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Biomedical subjects

S Igarashi

Publications and source records attributed to S Igarashi.

At least 19 recordsLinked to original sources

Estimation of the total saliva volume produced per day in five-year-old children.

Fifteen boys and 15 girls were asked to record for 2 days the time spent awake, eating meals or snacks, and sleeping. The salivary flow rates elicited by chewing foods were also determined. The mean flow rate (+/- SD) of unstimulated saliva was 0.26 +/- 0.16 ml/min and that of saliva while chewing six different foods was 3.6 +/- 0.8 ml/min. The mean times spent eating, and awake but not eating, were 80.8 +/- 27.3 and 820 +/- 59 min, respectively, and the volumes of saliva produced during those periods would average about 288 and 208 ml, respectively. If the flow rate is virtually zero during sleep, the estimated total salivary volume produced per day is calculated to be about 500 ml.

Child, Preschool

Interaction between activin A and cAMP in the induction of FSH receptor in cultured rat granulosa cells.

The acquisition of FSH receptor during preantral folliculogenesis is believed to be a key step in the subsequent development of follicles. We examined the interaction between activin and cAMP in FSH receptor induction in rat granulosa cells by measuring 125I-FSH binding and FSH receptor mRNA. In the 125I-FSH binding study, 0.2 mM 8-Br-cAMP and 1 microM forskolin were maximally effective in FSH receptor induction (169 and 220% respectively of control), while higher concentrations gave attenuated responses. It appears that cAMP has ambivalent effects on FSH receptor induction depending on the concentration and length of exposure. Activin alone dramatically increased the number of FSH receptors (314% of control). Moreover, synergistic effects of activin and 8-Br-cAMP or forskolin were observed on FSH receptor induction: a combination of activin (80 ng/ml) and low doses of 8-Br-cAMP (0.2 mM) or forskolin (1 microM) was most effective (160 or 140% of that induced by activin alone) and receptor levels reached a maximum at 24 h. These levels than markedly decreased after 72 h of incubation. Northern blot analysis revealed that the combination of activin (80 ng/ml) and 8-Br-cAMP (0.2 mM) or forskolin (1 microM) increased FSH receptor mRNA to about 140% of that induced by activin alone. These results indicate that activin and cAMP induced FSH receptor synergistically. However, activin did not enhance the production of cAMP induced by forskolin. In addition, a protein kinase A inhibitor (H89) (2 microM), which inhibited the effects of forskolin, had no effect on the action of activin.(ABSTRACT TRUNCATED AT 250 WORDS)

8-Bromo Cyclic Adenosine Monophosphate

Molecular cloning of a full-length cDNA for dentatorubral-pallidoluysian atrophy and regional expressions of the expanded alleles in the CNS.

Dentatorubral-pallidoluysian atrophy (DRPLA) is an autosomal dominant neurodegenerative disorder characterized by genetic anticipation and variable combinations of symptoms including myoclonus, epilepsy, cerebellar ataxia, choreoathetosis, and dementia. Recently, we discovered that DRPLA is caused by unstable expansion of a CAG repeat of a gene on the short arm of chromosome 12. We determined the consensus DRPLA cDNA sequence containing the complete coding region for 1,185 amino acids. The CAG repeat, which is expanded in DRPLA, is located 1,462 bp downstream from the putative methionine initiation codon and encodes a poly-glutamine tract. Although poly-serine and proline tracts exist near the CAG repeats, these polyserine or proline tracts did not show any polymorphisms, which is in strong contrast to the high heterogeneity in the length of the CAG repeat. Northern blot analysis revealed a 4.7-kb transcript that is widely expressed in various tissues including heart, lung, kidney, placenta, skeletal muscle, and brain. Reverse transcription-PCR analysis revealed that the expanded alleles are transcribed to levels comparable to those of normal alleles. These results indicate that there is no difference in transcriptional efficiency between expanded and normal alleles. Furthermore, mRNA from cerebellar hemispheres of DRPLA patients showed smaller sizes of CAG repeats compared with other regions of the brain, which reflects somatic mosaicism of the expanded alleles of the DRPLA gene.

Alleles

Preferential localization of c-kit product in tissue mast cells, basal cells of skin, epithelial cells of breast, small cell lung carcinoma and seminoma/dysgerminoma in human: immunohistochemical study on formalin-fixed, paraffin-embedded tissues.

Eighteen hundred and eighty-four cases of human solid tumours and 833 samples of normal human tissues, formalin-fixed and paraffin-embedded, were examined immunohistochemically for expression of c-kit oncogene product using polyclonal antibody against synthesized c-kit peptide. Seminoma/dysgerminoma and small cell lung carcinoma (SCLC) show preferential c-kit expression at 92% and 36% frequency, respectively, whereas only sporadic cases of cervical carcinoma and non-SCLC lung carcinoma show c-kit positivity. A normal tissue counterpart positive for c-kit product is detected in the testis (spermatocyte) and ovary (oocyte) but not in the lung or the cervix. In contrast, normal epithelial cells of the breast, skin basal cells and tissue mast cells harbour c-kit product, but transformed cells of the former two are largely deficient in the c-kit protein. One hundred and thirty-nine neuroendocrine tumours and 39 non-pulmonary small cell carcinomas were all negative, except for two cases of neuroblastoma. This indicates a distinct character for SCLC in c-kit expression. The c-kit product may be a useful marker in diagnostic pathology of seminoma/dysgerminoma and SCLC among human solid tumours, and in distinction of SCLC from non-pulmonary small cell carcinoma.

Adult

Cloning and sequencing of a rat type II activin receptor.

A full-length cDNA for a rat type II activin receptor was cloned by hybridization from a rat ovary cDNA library. The deduced amino acid sequence (513 residues) containing a single membrane-spanning domain and an intracellular kinase domain with predicted serine/threonine specificity. The amino acid sequence is 99.8% and 99.4% identical in the coding region with the previously cloned mouse and human type II activin receptor, and only 66.7% identical in the coding region with the previously cloned rat type IIB activin receptor. We examined the effect of PMSG-hCG on the mRNA level of type II activin receptor in immature rat ovaries. Northern blot analysis of ovarian RNA revealed two mRNAs (3.0 kb and 6.0 kb).

Activin Receptors

Substrate adhesiveness and experimental metastatic potential of rat ascites hepatoma AH7974-derived variant sublines.

Cells of an adherent subline (74AD, adhesion greater than 95%) and a floating subline (74FL, adhesion less than 1%) of rat ascites hepatoma AH7974 produced substrates containing fibronectin (FN), laminin (LN) and type IV collagen (CL-IV), with 74AD cells producing higher levels of each component. 74AD cells possessed high adhesion affinities to LN and CL-IV substrates. By contrast, 74FL cells hardly adhered to these purified attachment proteins. The difference in adhesion between the two lines in vitro tended to increase on incubation of the cells in medium containing fetal bovine serum. However, 74FL and 74AD cells adhered avidly to the extracellular matrix (ECM) of vascular endothelial cells. Although the cell-ECM adhesion apparently was not inhibited by pretreatment of the ECM with anti-FN, anti-LN and anti-CL-IV antibodies, the 74FL cell-ECM adhesion was inhibited considerably by pretreatment of the ECM with a mixture of these antibodies, especially with a combination of anti-FN and anti-LN antibodies. The lung-colonizing potential of 74FL cells was greater than that of 74AD cells, but the liver-colonizing potential of 74FL cells was less than that of 74AD cells. These results suggest that rat ascites hepatoma cells with extremely reduced substrate adhesiveness retain an adhesion mechanism that binds to FN and LN in the ECM of vascular endothelial cells. This mechanism may be a minimum essential unit of tumor cell-ECM adhesion in lung colonization, but the unit is insufficient for liver colonization of these cells.

Animals

Strong correlation between the number of CAG repeats in androgen receptor genes and the clinical onset of features of spinal and bulbar muscular atrophy.

X-linked spinal and bulbar muscular atrophy (SBMA), a motor neuron disease associated with androgen insensitivity, is caused by androgen receptor gene mutations with an increased number of tandem CAG repeats in exon 1. We investigated the increased number of CAG repeats in androgen receptor genes of 19 SBMA patients and found that this correlated strongly with the age at onset of muscle weakness. Thus, SBMA is the first genetic disease in which a strong correlation between the degree of genetic abnormality (number of CAG tandem repeats) and clinical phenotypic expression is demonstrable. The results further indicate that androgen gene mutation is directly involved in the degeneration of motor neurons.

Adult

Comparison of the distribution of carbonic anhydrase isozymes (CA-I, CA-II, CA-III) in the rat gastrointestinal tract.

The present paper described the immunohistochemical distributions of carbonic anhydrase (CA) isozymes. CA-I, CA-II and CA-III, in the epithelium lining the rat gastrointestinal tract, with rabbit antibodies to equine CA-I, CA-II and CA-III. Prior to the immunohistochemical examinations, the crossreactivities of these antibodies to the rat-antigens were confirmed in this study. In the stomach, surface epithelial cells and parietal cells of the glandular region showed an immunoreactivity only to CA-II. In the large intestine, each immunoreactivity to CA isozyme (CA-I, CA-II and CA-III) was localized in the upper portion of intestinal glands, and decreased toward the distal digestive tract, but absent in the small intestine. The present histological findings suggested that the CA isozymes might play a role in the ion-transportation during the water absorption in the rat large intestine.

Animals

Paraneoplastic cerebellar degeneration: successful early detection and treatment of cancer through characterization of the anti-Purkinje cell antibody.

Paraneoplastic cerebellar degeneration (PCD) is thought to be caused by an autoantibody against both tumor and neuronal tissue. Such autoantibodies are most frequently detected in patients with gynecological or breast cancer, and are designated as anti-Yo. We report here a patient with PCD whose underlying cancer could not be detected despite extensive tumor survey. IgG in her serum and cerebrospinal fluid reacted with the cytoplasm of cerebellar Purkinje cells immunohistochemically. On immunoelectron microscopy, the endoplasmic reticulum and Golgi complex were stained. Her IgG bound to the 58 kD band on immunoblots of cerebellar proteins. A reaction was also observed with the recombinant proteins deduced from the complementary DNA clone encoding a neuronal cell antigen reported by Sakai et al (Ann Neurol 28: 692, 1990). Based on these results, successful early resection of fallopian tube adenocarcinoma was performed. It is crucially important to characterize these PCD related autoantibodies for the early treatment of underlying malignant tumors.

Adenocarcinoma

Mercury deposition and its relationship to inner ear function in methylmercury-poisoned rats. A histological and immunohistochemical study.

Mercury deposition and its relationship to the inner ear function in methylmercury-poisoned rats were examined. Rats were poisoned with methylmercury chloride. After the appearance of signs of poisoning, the cerebellar and inner ear tissues were examined histochemically using an autoradiographic procedure. Mercury deposits were typically found in the cerebellum and appeared in parts of the vestibular nerves, cochlear nerves, spiral ganglion and stria vascularis. In the vestibule, a slight mercury deposition was observed in the acoustic maculae and in the cochlea; only one instance of mercury deposit in the organ of Corti was detected. The effect of mercury on the inner ear function was also assessed on the basis of immunohistochemical localization of substance P which is believed to be a neurotransmitter in the inner ear. However, no pathological changes were detected. These findings suggest that methylmercury deposition has little effect on the inner ear function.

Animals

[A mother and her son with autosomal dominant bulbar spinal muscular atrophy].

We reported a 49-year-old mother and her 28-year-old son with autosomal dominantly inherited bulbar spinal muscular atrophy (AD-BSMA). They showed progressive bulbar paresis, muscle wasting and weakness dominant in the proximal groups of limb muscles, and finger tremor. Onset of illness was in adult life. In laboratory examinations, elevated creatine kinase in serum and neurogenic changes either in EMG or muscle biopsy were noted. The son had neither gynecomastia nor abnormal sexual hormone levels which were observed in the sex-linked recessive bulbar spinal muscular atrophy (SR-BSMA). Elongation due to the CAG repeats at the androgen receptor gene of the X chromosome in SR-BSMA was not detected. In conclusion, it is clear that AD-BSMA is different from SR-BSMA on the basis of clinical and genetical aspects.

Adult

[Rapid diagnosis of tuberculous meningitis by polymerase chain reaction (PCR)].

Using polymerase chain reaction (PCR), a rapid and highly sensitive method was developed for the diagnosis of tuberculous meningitis. The mycobacterium tuberculosis (M. tuberculosis) genome was detected in CSF of 5 of 6 patients with clinically diagnosed tuberculous meningitis, but not present in CSF from 10 patients with other types of meningitis and 10 normal controls. Furthermore, we detected M. tuberculosis in CSF of 2 of 24 patients with clinically possible tuberculous meningitis. This is highly useful method for the rapid diagnosis of tuberculous meningitis over other conventional method.

Adult

[A case of paraneoplastic cerebellar degeneration--success in early detection of cancer by anti-Purkinje cell antibody].

A 70-year-old woman was admitted to our hospital because of rapidly progressive cerebellar ataxia. Neurological examinations showed saccadic eye movement, downbeat nystagmus, scanning speech, proximal dominant muscle weakness and severe truncal and limb ataxia. Based on these clinical features, she was suspected to have paraneoplastic cerebellar degeneration (PCD), although the malignant tumor was not detected through clinical intensive surveys. Her serum and CSF revealed to have anti-Purkinje cell antibodies immunohistochemically, and western blot analysis showed that they reacted with 58 kd band. In view of previous reports of PCD, she was strongly suspected to have gynecological cancers. The trial laparotomy found early stage fallopian tubal cancer, which had not been detected by CT scan, ultrasonogram and MRI. It is important to detect and characterize these autoantibodies found in the PCD patients for early diagnosis and treatment of underlying cancer.

Aged

[A case of myasthenia gravis complicated by cyclic thrombocytopenia].

A 47-year-old woman with myasthenia gravis for last 11 years was admitted because of relapsed muscle weakness, hypermenorrhea and thrombocytopenia. Physical and neurological examinations revealed diplopia, proximal muscle weakness and purpuras on the left arm and bilateral legs. Repeated hematological examinations revealed cyclic fluctuation of platelet counts which spontaneously changed from the nadir levels of 12-27 x 10(3)/microliters to the peak levels of 150-400 x 10(3)/microliters. The platelet count reached a nadir at the onset of menstruation. Platelet-associated IgG (PAIgG) was within normal level when platelet count was at an increasing phase. Survival time of autologous platelets was normal when platelet count was at an increasing phase. Megakaryocytes in the bone marrow were apparently normal at the nadir phase. The patient's serum obtained at the nadir of platelet count significantly suppressed megakaryocyte colony forming unit (Meg-CFU) formation in comparison with that after the stabilization of platelet count, suggesting that this cyclic thrombocytopenia was secondary to cyclic hypoproduction of megakaryocytes caused by a suppressive factor. On the other hand muscle weakness showed no cyclic fluctuation. Administration of 60 mg/day prednisolone stabilized the platelet count at about 280 x 10(3)/microliters, abolished hypermenorrhea and gradually improved muscle weakness. These findings suggested autoimmune mechanism in the production of a Meg-CFU-suppressive factor might be involved in the pathogenesis of thrombocytopenia.

Female

Developmental changes in the ferret ileum during the postnatal period.

The development of the ferret ileum was studied in order to determine the pattern of morphological maturation during the postnatal period. In the newborn, intestinal villi were short, and lined by simple columnar enterocytes with striated borders and small vacuoles. At one week old, the equivalent cell had large vacuoles that were shown on TEM to be related to a tubulovesicular system in the apical region of the cytoplasm. At two and three weeks old, the epithelial cells at the same site showed a more extensive tubulovesicular system, and vacuoles occupied major areas of both the supra- and subnuclear cytoplasm. At six weeks old (weaning), although the enterocytes contained a few small intracellular vesicles, they appeared histologically more mature than in previous stages. At nine weeks and in the adult, the villi were longer and the enterocytes no longer contained vacuoles. In TEM, the epithelial cells had long microvilli, and the apical tubulovesicular system and vacuoles had completely disappeared from the cytoplasm.

Animals