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Biomedical subjects

S Mori

Publications and source records attributed to S Mori.

At least 19 recordsLinked to original sources

An immunohistologic evaluation of C-erbB-2 gene product in patients with urinary bladder carcinoma.

BACKGROUND: Amplification or overexpression of the c-erbB-2 gene have been reported to correlate with poor patient prognosis in human breast, gastric, and ovarian cancer. Recently, the c-erbB-2 gene product was found to be expressed frequently in the urinary bladder carcinoma. In the current study, the presence of the c-erbB-2 gene product in urinary bladder carcinomas was compared with patient outcome to evaluate whether c-erbB-2 gene product could identify a subset of patients who are destined to have a poor prognosis. METHODS: Immunohistologic study of the c-erbB-2 gene product was done in formaldehyde-fixed paraffin-embedded tissue specimens obtained from 88 transitional cell carcinomas of the human urinary bladder. Eighty-three patients who underwent complete tumor resection by total cystoprostatectomy (30 patients) or by bladder-preserving operations such as transurethral surgery (50 patients) or partial cystectomy (3 patients) entered a follow-up study. The other five patients did not enter the follow-up study because of lost follow-up (2 patients) or distant metastasis at the time of surgery. RESULTS: The c-erbB-2 gene product was expressed in 23 of 88 patients (26%), showing an increase in the expression rate corresponding to the advancement of tumor grade (P < 0.05) and tumor stage (P < 0.2). The 5-year disease-free survival rate was 48.5% for patients with c-erbB-2 negative tumors versus 9.7% for those with c-erbB-2 positive tumors (P < 0.01). The 5-year actuarial survival rate was 65.5% for patients with c-erbB-2 negative tumors versus 41.8% for those with c-erbB-2 positive tumors (P < 0.05). Multivariate analysis using Cox regression model showed that the c-erbB-2 gene product tissue status was a significant prognostic factor independent of grade and stage of the tumor. CONCLUSIONS: The results suggest that the c-erbB-2 gene product could be a tumor marker to identify a malignant subgroup in bladder carcinomas.

Adult

Polymerase chain reaction for the detection of the varicella-zoster genome in ocular samples from patients with acute retinal necrosis.

We used the polymerase chain reaction to detect the virus genome in ocular samples from patients with clinically diagnosed acute retinal necrosis. Four samples from four patients with acute retinal necrosis, and five samples from three patients with other ocular diseases (sarcoidosis, rhegmatogenous retinal detachment, and epiretinal membrane of unknown origin) were evaluated. The samples consisted of aqueous humor, vitreous, or subretinal fluid. Primers were specific for varicella-zoster virus, herpes simplex virus, or cytomegalovirus. The varicella-zoster virus genome was detected in three of the four samples from patients with acute retinal necrosis. Among these three positive samples, two had PstI-site-less point mutation, strains that have been described only in Japan and of low prevalence. Samples from patients with diagnoses other than acute retinal necrosis yielded negative results when varicella-zoster virus primer was used. No sample was positive for herpes simplex virus or cytomegalovirus primers.

Adult

Correlation between the serum level of hepatitis C virus RNA and disease activities in acute and chronic hepatitis C.

The influence of viremia on hepatic injury in patients infected with hepatitis C virus was examined by analysis of the relationship between alanine aminotransferase activity and the amount of hepatitis C virus RNA in sequential serum samples from I untreated patient with acute hepatitis C and 3 untreated patients with chronic hepatitis C. Semiquantitative analysis by the competitive-reverse-transcription/polymerase-chain-reaction method indicated that the quantity of hepatitis C virus RNA in the serum affected the disease activities of acute and chronic hepatitis C through their natural clinical courses in all these patients. The nucleotide sequence encoding the putative envelope region of the viral genome in the patient with acute hepatitis C was examined. Blood samples taken serially at 2 times of exacerbation of the hepatitis revealed 2 nucleotide mutations, resulting in changes of predicted amino acid residues. This finding suggests that nucleotide mutations in the envelope region of the viral genome may be responsible for the recurrent hepatic injury attributed to recurrence of viremia in patients with hepatitis C. From these aspects, the serial divergence of the virus genome in infected individuals, especially in the region encoding the viral envelope protein, may possibly play an important role in developing chronic infection of hepatitis C virus.

Amino Acid Sequence

A point mutation of c-Ki-ras gene was found in human esophageal carcinoma cell lines but not in primary esophageal carcinomas.

Activation of the ras oncogene in primary human esophageal carcinomas and cell lines established from such carcinomas was analyzed using the polymerase chain reaction (PCR)-direct sequencing method. This analysis revealed a GC----AT transition at the second base in the 12th codon of the c-Ki-ras gene in TE1 and TE2 esophageal carcinoma cell lines. In contrast, no point mutation was detected in the 12th, 13th, and 61st codon of the c-Ki-ras and c-Ha-ras gene in 31 primary esophageal carcinomas including those from which TE1 and TE2 cell lines were established. These results demonstrate that while activation of the c-Ki-ras gene by point mutation occurred in a subset of esophageal carcinoma cell lines during establishment of the cell lines, the activation events are not important in the transformation of human esophageal epithelial cells.

Adenocarcinoma

An aromatase-associated cytoplasmic inclusion, the "stigmoid body," in the rat brain: I. Distribution in the forebrain.

An aromatase-containing neural system was examined in the rat forebrain, using a polyclonal antibody against aromatase-associated human placental antigen X-P2 (hPAX-P2). Numerous dot-like structures, which we have called stigmoid bodies, were immunostained in the preoptico-hypothalamic region, the bed nucleus of the stria terminalis, the medial amygdala, the arcuate nucleus, the subfornical organ, and the area extending from the hypothalamic area to the central gray through the medial forebrain bundle and the periventricular fiber system of the posterior diencephalon. The stigmoid bodies were always found as inclusions in the neuronal cytoplasm. Their diameter was usually 1-3 microns, but exceptionally large forms, over 3 microns, were found in some brain regions, including the area extending from the median preoptic nucleus surrounding the organosum vasculosum laminae terminalis to the anterior medial preoptic nucleus, the periventricular nucleus of the preoptic area, and some parts of the medial preoptic nucleus. Most of these nuclei show sexual dimorphism. The distribution pattern of the hPAX-P2 immunoreactive stigmoid bodies agreed well with that of aromatase activity previously reported in many biochemical studies. Brain regions where the stigmoid bodies were prominent largely coincide with steroid binding locations common to both androgen and estrogen, or regions where both sex steroid receptors are present. Although it still remains to be determined whether aromatase is localized within these stigmoid bodies, it appears likely that they are closely associated with the function of sex steroids at their target sites in the brain.

Animals

Uveitis associated with human T-cell lymphotropic virus type I.

Seroepidemiologic, clinical, and virologic studies were performed to determine whether human T-cell lymphotropic virus type I was closely associated with uveitis in two hospitals. One hospital was in an endemic area of the virus (Miyakonojo, Miyazaki) and the other hospital was in a less endemic area (Kurume). In the endemic area, the seroprevalence of the virus in patients with uveitis without defined causes (35.4%, 62 of 175 patients) was significantly higher than that in patients with nonuveitic ocular diseases (16.1%, 42 of 261 patients), or in patients with uveitis with defined causes (10.3%, eight of 78 patients). The seroprevalence in younger patients (20 to 49 years of age) with uveitis without defined causes in the area was 44.8% (30 of 67 patients), whereas it was only 9.3% (ten of 107 patients) in the other two groups. A similar observation was recorded even in the less endemic area (Kurume). Because the seroprevalence of the virus in the general population is known to be low in younger patients and to increase with age, these findings were interpreted to indicate that the association of human T-cell lymphotropic virus type I with uveitis was significant. Most patients, particularly those aged 20 through 49 years, had an intermediate uveitis characterized by a moderate inflammation in the vitreous body accompanied by an iritis and retinal vasculitis. The ocular symptoms in the patients differed from those of other types of uveitis common in Japan (Behçet's disease, Vogt-Koyanagi-Harada's disease, and toxoplasmosis, for example).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Hyaluronate synthesized by cultured skin fibroblasts derived from patients with Werner's syndrome.

Hyaluronate in cultured skin fibroblasts derived from patients with Werner's syndrome, who excrete large amounts of urinary hyaluronate, was investigated. The amount of hyaluronate secreted into the medium by Werner's fibroblasts was 2-3-times that of normal fibroblasts, whereas no difference in enzyme activities related to the degradation of hyaluronate was found. Werner's fibroblasts were then cultured in the presence of [3H]glucosamine, and the amount of [3H]hyaluronate and its chain lengths in the medium and matrix (trypsinate) fractions were compared with those of normal cells. No significant difference in the chain length of hyaluronate was observed between normal and Werner's fibroblasts. On the other hand, a significant increase of hyaluronate was found in the matrix fraction of Werner's fibroblasts when the cells reached confluency. In addition, a hyaluronate of small chain length was found in the matrix fraction of Werner's fibroblasts, although this was absent from that of normal cells. It was concluded that the constituents of the extracellular matrix of Werner's fibroblasts differed from those of normal cells, characterized by the presence of a large amount of hyaluronate and a relatively small hyaluronate chain.

Adult

Ligand-induced polyubiquitination of the platelet-derived growth factor beta-receptor.

We have analyzed the nature of ligand-induced shift to higher molecular weight forms of the beta-receptor for platelet-derived growth factor expressed in porcine aortic endothelial cells. The modification of the beta-receptor was found to be due to polyubiquitination, as judged by immunoblotting using an anti-ubiquitin antiserum. A mutant beta-receptor made kinase negative by a point mutation (K634A mutant) did not undergo ubiquitination in response to ligand stimulation. A mutant in which carboxyl-terminal 98 amino acids were deleted (CT98 mutant) and which retained kinase activity was likewise not ubiquitinated. These data suggest that the kinase activity, as well as the carboxyl-terminal 98 amino acids, is required for ubiquitination of the beta-receptor. Ligand-induced degradation of the receptor-bound ligand, as well as of the receptor itself, was partially impaired in the CT98-receptor-expressing cells, suggesting that the ubiquitination is of importance for efficient degradation of the ligand-receptor complex.

Animals

Clinicopathologic and therapeutic aspects of angioimmunoblastic lymphadenopathy-related lesions.

The clinicopathologic features of 14 patients with angioimmunoblastic lymphadenopathy (AIL)-related lesions were analyzed. Lymph node biopsy specimens from all the patients showed a diffuse obliteration of lymph node architecture, prominent vascular proliferation, a polymorphous cellular infiltrate, including immunoblasts, and varying degrees of clear cell proliferation. The patients were eight males and six females, with a median age of 58.5 years. All but one were in an advanced stage at the time of diagnosis. Bone marrow involvement was observed in eight patients. Thirteen patients had a negative serologic reaction for antibody to human T-cell leukemia virus type I (HTLV-I), and one patient was considered to be a HTLV-I carrier. Polyclonal hypergamma-globulinemia was observed in 6 patients, and 6 of the 12 patients showed elevated IgE levels. Immunophenotyping of the involved lymph nodes revealed a preponderance of T-cells in all the patients. Eleven of these patients showed a predominance of CD4+ over CD8+ T-cells, and only one patient showed a predominance of CD8+ over CD4+ T-cells. Two of five patients whose gene analysis was carried out showed clonal rearrangement of the T-cell receptor beta chain gene without rearrangement of the immunoglobulin heavy chain genes. Twelve patients received doxorubicin-containing combination chemotherapy; of these, 7 patients achieved complete response, and the other 5 had partial response. Nine patients are still alive with a median follow-up period of 21 months, and five patients died during the follow-up period. Progression to high-grade T-cell lymphoma with systemic infiltration was ascertained in two of three cases for which autopsy was performed. From our experience, we recommend doxorubicin-containing combination chemotherapy as initial therapy for AIL-related lesions.

Aged

A new type of hepatitis C virus in patients in Thailand.

Partial nucleotide sequences in the tentative NS5 region of the hepatitis C viral genome obtained from patients with chronic hepatitis in Thailand were analyzed by reverse transcription followed by the polymerase chain reaction. Of ten samples studied, four showed low homologies to any known type of HCV: the homologies of the nucleotide sequences of these clones with HCV-J, -US, -K2a and -K2b were 66.5-69.1%, 66.5-68.2%, 61.2-64.1% and 64.4-66.2%, respectively, and the homologies of their deduced amino acids sequences were 71.7-75.2%, 71.7-75.2%, 69.0-72.6% and 69.9-73.5%, respectively. These four clones were classified a new distinct type of HCV, named HCV-T. Moreover, the nucleotide and amino acid sequence homologies of the four HCV-T clones showed that the HCV-T type could be classified into two genotypes, HCV-Ta and HCV-Tb.

Amino Acid Sequence

The changes in the activity of pudendal motoneurons in relation to reflex micturition evoked in decerebrate cats.

Reflex micturition was evoked in both non-immobilized (n = 5) and immobilized (n = 5) decerebrate cats by filling the bladder with physiological saline. Intracellular recordings were made from pudendal motoneurons (PU-MNs; n = 14) throughout the periods of before, during and after reflex micturition. The changes in the activity of PU-MNs were correlated with those in the intravesical pressure. Our results support the proposition that coordination of the sphincters and the detrusors is established by a gating mechanism, which is activated by the supraspinal source such as the pontine micturition center.

Animals

Developmental changes in the serotoninergic innervation of hindlimb extensor motoneurons in neonatal rats.

The postnatal development of quadriceps femoris motoneurons (Q-MNs) and serotonin (5-HT) nerve terminals in rat spinal cord were studied using retrograde neurotracing techniques combined with 5-HT immunohistochemistry. We attempted to elucidate the 5-HT-ergic innervation to the Q-MNs by counting the number of 5-HT-immunoreactive varicosities that were in close apposition to the Q-MNs. The following results were obtained: (1) Q-MNs possessed, at birth, few if any very short dendrites. The size of these somata was relatively uniform and small. During postnatal periods lasting from 1 to 30 days, the mean cell size of Q-MNs increased with the development of dendrites. From 5 to 14 days after birth, in particular, cell size increased markedly. (2) 5-HT-immunopositive fibers were, at birth, already observed in the ventral horn of the lumbar spinal cord. The density of these fibers increased gradually with age. (3) At birth, only a few 5-HT terminals and varicosities showed close apposition with about half the Q-MNs examined. At 5-days postnatally, such close apposition was found in all Q-MNs. By the first two postnatal weeks, Q-MNs grew quickly and the 5-HT innervation to the Q-MNs appeared to have been established. Based on these results, the significance of 5-HT innervation to developing Q-MNs is discussed in relation to the postnatal development of motor function.

Animals

Tetraparental mice reveal complex cellular interactions of the mutant, autoimmunity-inducing lpr gene.

Lpr is a murine recessive autosomal mutant gene that, in conjunction with the background genes of different inbred mouse strains, produces varied syndromes of lymphadenopathy and autoantibody production. We have investigated the cellular basis of the lpr determined phenomena by constructing allophenic (tetraparental) chimeras of MRL/Mp-lpr/lpr combined with C57BL/6 and MRL/+ combined with C57BL/6-lpr/lpr. The appearance of lymphadenopathy, lpr atypical T cells, and autoantibodies was found to depend on the relative amounts +/+ and lpr tissue. The failure of these three abnormalities to correlate in certain animals suggested different pathways of lpr gene action. Furthermore, in the lpr predominant animals, both the lymphadenopathy and autoantibodies were essentially entirely contributed by the lpr donor. The expression of the lpr gene within the same cells expressing the MRL or B6 background determined the pathologic and serologic manifestations characteristic of the disease of that lpr strain, despite the presence of +/+ cells of the other background in the same individual. The lpr syndrome thus depends on the intracellular interaction of the lpr and background genes, and on positive signalling between different lpr cell populations.

Animals

Identification of two C-terminal autophosphorylation sites in the PDGF beta-receptor: involvement in the interaction with phospholipase C-gamma.

Two novel sites of autophosphorylation were localized to the C-terminal tail of the PDGF beta-receptor. To evaluate the importance of these phosphorylation sites, receptor mutants in which Tyr1009, Tyr1021 or both were replaced with phenylalanine residues, were expressed in porcine aortic endothelial (PAE) cells. These mutants were similar to the wild type receptor with regard to protein tyrosine kinase activity and ability to induce mitogenicity in response to PDGF-BB. However, both the Y1009F and Y1021F mutants showed a decreased ability to mediate association with and the tyrosine phosphorylation of phospholipase C-gamma (PLC-gamma) compared to the wild type PDGF beta-receptor; in the case of the Y1009F/Y1021F double mutant, no association or phosphorylation of PLC-gamma could be detected. These data show that tyrosine phosphorylation of PLC-gamma is dependent on autophosphorylation of the PDGF beta-receptor at Tyr1009 and Tyr1021.

Amino Acid Sequence

Variability of laminin immunoreactivity in human autopsy brain.

Laminin immunoreactivity is thought to be masked in formalin-fixed sections since proteolytic treatment is required to unmask it. We analyzed this masking with frozen and formalin-fixed human autopsy brains obtained at various postmortem periods. In unfixed, frozen sections, intense immunoreactivity was invariably detected in vascular walls of entire sections. When such sections were postfixed in formalin, immunoreactivity was not diminished even after prolonged fixation. In vibratome sections of brain fixed in formalin in situ, immunoreactivity varied with postmortem delay: in most cases, immunoreactivity was weak and restricted to superficial cortical layers. However, the extent of immunoreactivity increased with postmortem delay. Two cases fixed after prolonged postmortem periods revealed moderate immunoreactivity throughout the sections. We also investigated rat brains processed without postmortem delay. In unfixed frozen sections, immunoreactivity again was observed throughout the sections, independent of the length of any postfixation. In vibratome sections of fixed rat brain, immunoreactivity was restricted to the cutting margins of the brain blocks and around a trauma-induced cortical lesion, regardless of how long the blocks had been kept in fixative. Our data suggest that postmortem proteolysis accomplishes similar unmasking of laminin antigen as digestion on paraffin sections and that such unmasking can also be effected by proteolysis induced by damaging tissue during cryostat sectioning of fresh tissue.

Adult

Effects of long-term daily administration of prostaglandin-E2 on maintaining elevated proximal tibial metaphyseal cancellous bone mass in male rats.

The effects of long-term prostaglandin E2 (PGE2) on cancellous bone in proximal tibial metaphysis were studied in 7-month-old male Sprague-Dawley rats given daily subcutaneous injections of 0, 1, 3, and 6 mg PGE2/kg/day and sacrificed after 60, 120, and 180 days. Histomorphometric analyses were performed on double fluorescent-labeled undecalcified bone specimens. After 60 days of treatment, PGE2 produced diffusely labeled trabecular bone area, increased trabecular bone area, eroded and labeled trabecular perimeter, mineral apposition rate, and bone formation rate at all dose levels when compared with age-matched controls. In rats given PGE2 for longer time periods (120 and 180 days), trabecular bone area, diffusely labeled trabecular bone area, labeled perimeter, mineral apposition, and bone formation rates were sustained at the elevated levels achieved earlier at 60-day treatment. The eroded perimeter continued to increase until 120 days, then plateau. The observation that continuous systemic PGE2 administration to adult male rats elevated metaphyseal cancellous bone mass to 3.5-fold of the control level within 60 days and maintained it for another 120 days indicates that the powerful skeletal anabolic effects of PGE2 can be sustained with continuous administration.

Animals

Production of new trabecular bone in osteopenic ovariectomized rats by prostaglandin E2.

Serum chemistry and bone morphometry of the proximal tibial metaphysis were performed in 3-month-old double fluorescent-labeled, female Sprague-Dawley rats subjected to bilateral ovariectomy or sham surgery for 4 months prior to treatment with 0, 0.3, 1, 3, or 6 mg of prostaglandin E2 (PGE2)/kg/day subcutaneously for 30 days. The 4-month postovariectomized rats possessed an osteopenic proximal tibial metaphysis with 7% trabecular area compared with controls (19%). PGE2 treatment elevated osteocalcin levels and augmented proximal tibial metaphyseal bone area in ovariectomized and sham-operated rats. Osteopenic, ovariectomized rats treated with 6 mg PGE2/kg/day for 30 days restored bone area to levels of age-matched sham-operated rats. Morphometric analyses showed increased woven and lamellar bone area, fluorescent-labeled perimeter (osteoblastic recruitment), mineral apposition rate (osteoblastic activity), bone formation rate (BFR/BV), and longitudinal bone growth. These dramatic bone changes were all significantly increased at the dose-response manner. This study showed that in vivo PGE2 is a powerful activator of bone remodeling, it increases both bone resorption and bone formation, and produces an anabolic effect by shifting bone balance to the positive direction. Furthermore, PGE2-induced augmentation of metaphyseal bone area in ovariectomized rats was at least two times greater than in sham-operated rats.

Alkaline Phosphatase