Biomedical subjects

M Kitagawa

Publications and source records attributed to M Kitagawa.

At least 145 records · Page 8Linked to original sources

PubMed1999

The role of the spleen, especially regarding changes in both thromboxane A2 and the remnant liver dysfunction after extensive hepatectomy.

The plasma levels of thromboxane B2 (TxB2) and 6-keto-prostaglandin F1alpha (6-KF) in the peripheral and portal blood increase after an extensive hepatectomy, and even more so in cases with complications. In this cell biological study, we estimated the prostanoids in the portal system to clarify which organ produces them, while also evaluating the effect of a splenectomy in conjunction with an extensive hepatectomy. Our results showed that the level of TxB2 in the splenic vein was significantly higher than that in the mesenteric vein. Furthermore, the TxA2 produced by splenic macrophages after an extensive hepatectomy was significantly more than after a sham operation. We also observed the hepatocyte damage to be less in the group that underwent an 84% hepatectomy and splenectomy than in the group that underwent the same hepatectomy without a splenectomy. It therefore appears important both to suppress the splenic macrophages from producing TxA2 and to prevent remnant hepatic dysfunction after an extensive hepatectomy.

6-Ketoprostaglandin F1 alpha↗

PubMed1999

Acute intermittent porphyria with central pontine myelinolysis and cortical laminar necrosis.

Acute intermittent porphyria (AIP) is an autosomal-dominant disease caused by a deficiency of porphobilinogen (PBG) deaminase. Patients with AIP present with neurological syndromes such as autonomic neuropathy, peripheral axonal neuropathy or central nervous system dysfunction. We report serial MRI of a patient with AIP who had cortical and subcortical cerebral changes. A 29-year-old woman with a 6-month history of AIP had an attack with severe hyponatraemia and generalised convulsions, treated with haem arginate and supportive therapy. MRI showed central pontine and extrapontine myelinolysis and cortical laminar necrosis. These are not common in AIP, but are likely to have been caused by rapid correction of hyponatraemia and by vasospasm, which could be induced by AIP.

Adult↗

PubMed1999

Protection of retrovirus-induced disease by transplantation of bone marrow cells transduced with MuLV env gene via retrovirus vector.

Fv-4 is a mouse gene that dominantly confers resistance to infection by ecotropic murine leukemia virus (MuLV). We have demonstrated previously that bone marrow chimeras in which hematopoietic cells were replaced with cells expressing Fv-4 resistant (Fv-4r) gene product became refractory to Friend leukemia virus (FLV)-induced leukemogenesis. To induce in vivo resistance against retrovirus-induced diseases by retroviral vector-mediated gene transduction, we introduced Fv-4 env gene into bone marrow cells of FLV-susceptible C3H/He (C3H) mice with retroviral vector (pLSF) derived from murine Friend spleen focus forming virus (SFFV) and the cells were transplanted into lethally irradiated C3H mice. After the bone marrow transplantation, Fv-4r gene product was successfully expressed on erythroid and myeloid cells, while lymphoid cells were only weakly expressing Fv-4r gene product. The C3H mice expressing relatively higher amounts of Fv-4r gene product were rendered resistant to FLV-induced erythroleukemia, while mice expressing lower amounts of the Fv-4r gene product were still susceptible. Effective protection of FLV-induced leukemia in these mice suggested that the Fv-4r gene expression by erythroid cells that were the major target of FLV infection might be critical for resisting FLV-induced leukemia. Thus, gene therapy model by transducing Fv-4r env gene using bone marrow transplantation would provide a useful protection model system of retrovirus-induced diseases.

Animals↗

PubMed1999

Age-related alteration of cytokine production profile by T cell subsets in mice: a flow cytometric study.

Spleen cells from young and old C57BL/6 mice were stimulated with a combination of anti-CD3 and anti-CD28 antibodies, and the profile of cytokine production was examined by two different methods; the concentrations of cytokines as measured by ELISA, and identification of cytokine-positive cells by flow cytometry. The ELISA method revealed that IL-2 production by spleen cells after stimulation was significantly lower in the old mice compared to the young mice. while IFN-gamma production was the reverse. The flow cytometric analysis showed that the percentage of IL-2 positive cells in spleen cells after the stimulation was significantly lower in the older mice than in the young mice, and vice versa for the percentage of IFN-gamma-positive cells. Regarding the T cell subsets, CD4+ T cells were a major source of IL-2 in both the young and old mice. IL-2-positive cells in both CD4+ and CD8+ T cells showed a significant decrease with age. On the contrary, CDX T cells were the major source of IFN-gamma. An age-related increase of IFN-gamma positive cells was observed in both CD4+ and CD8+ T cells. CD4 T cells were the major source of IL-4, and the percentage of IL-4-positive CD4+ T cells also increased with age, although the level of IL-4 production was modest in C57BL/6 mice compared with IL-2 and IFN-gamma. Such age-related changes of cytokine production are presumed to play an important role in the alteration of immunological capacity with age.

Aging↗

PubMed1999

Vitamin E enhances the immune functions of young but not old mice under restraint stress.

Young and old C57BL/6 male mice were given a diet containing a high dose of vitamin E (VE treatment) and its effect on the immune system was examined before and after the exposure to restraint stress. The VE treatment per se gave rise to a slight increase of splenic T cells in percentage and a significant enhancement of Con A response of spleen cells in young, but not in old mice. The VE treatment also resulted in the enhancement of production of IL-2 and IFNgamma in young, but not in old mice. Restraint stress led to thymic involution in both young and old mice. This thymic involution was not ameliorated by the VE treatment. Percentage of splenic T cells and their mitogenic response decreased just after the stress, but soon rebounded over the control level. The VE treatment further enhanced the recovery after the stress in young mice, but on the contrary suppressed the recovery in old mice. The results in the present study suggested that the VE treatment was effective in the prevention of immunological decline of young mice before and after the exposure to the stress. On the other hand, such a preventive effect was not observed in old mice that were already in the depressed state of immunological functions.

Aging↗

PubMed1999

Molecular understanding of chronic pancreatitis: a perspective on the future.

Despite the recent development of medical imaging technology, chronic pancreatitis can only be diagnosed when the disease is fully established. This is due to the lack of specific and sensitive markers for this disease. The discovery of mutations in the cationic trypsinogen gene in patients with hereditary pancreatitis and a high incidence of mutations in the cystic fibrosis transmembrane conductance regulator gene in patients with chronic pancreatitis might be important clues to understanding the molecular mechanisms of this disease. The interaction between ethanol and ion channels might be the missing link between alcohol ingestion and chronic pancreatitis.

Adult↗

PubMed1999

Expression of inducible nitric oxide synthase (NOS) in bone marrow cells of myelodysplastic syndromes.

Nitric oxide (NO) is a biological mediator which is synthesized from L-arginine by a family of nitric oxide synthases (NOS). We have studied the expression of the inducible NOS (iNOS) by bone marrow cells from the patients with myelodysplastic syndromes (MDS) at the mRNA level by RT-PCR assay and at the protein level by immunohistochemical staining using a specific anti-iNOS monoclonal antibody. The iNOS message was present in 92% of bone marrow tissues from MDS patients (11 out of 12) by an examination using RT-PCR. Basically, iNOS message was negative or very weak in control (1/9) and AML (0/7) cases. This was supported by immunohistochemical findings that the iNOS was positive in most of the bone marrow samples from MDS patients (9 out of 12), while bone marrow cells of control (O out of 12) and AML (O out of 5) cases were basically negative. Double immunostaining for CD68 antigen, which is a marker for macrophage lineage cells, and iNOS was performed on MDS bone marrow sections. iNOS was dominantly localized to bone marrow macrophages, although a part of myeloid cells were also positively stained with anti-iNOS antibody in a part of cases. These results indicated that there is some in vivo induction of iNOS expression for local NO production that might be involved in the dysregulation of hematopoiesis in bone marrow of MDS.

Adult↗

PubMed1999

Case report: Hepatocellular carcinoma in type 1a glycogen storage disease with identification of a glucose-6-phosphatase gene mutation in one family.

A 40-year-old man with glycogen storage disease type 1a (von Gierke disease, GSD1a) developed hepatocellular carcinoma (HCC). Cold single-strand conformation polymorphism (SSCP) with 12% glycerol identified the G727T mutation in the glucose-6-phosphatase (G6Pase) gene, which has been reported to be the most common mutation in Japanese GSD1a patients. This case report is the first documentation of HCC in a case with G727T mutation. Given the prevalence of HCC in GSD1a with various germline mutations, analysis is needed to confirm that the germline mutation in this case is really related to hepatocarcinogenesis. DNA analysis of the family pedigree of this case, revealed three individuals with GSD1a and seven heterozygous carriers of the G727T mutation. As the diagnosis of GSD1a in this family was made only after these three patients reached adulthood, DNA diagnosis may help early identification of GSD1a patients and prevention of the progression of the disease. This DNA-based diagnosis permits prenatal diagnosis in at-risk patients and may facilitate screening and counselling of patients clinically suspected of having this disease.

Adolescent↗

PubMed1999

Collagen secretion and growth of mesangial cells require geranylgeranylpyrophosphate.

BACKGROUND: The mevalonate pathway is important for the biosynthesis of isoprenoids such as geranylgeranylpyrophosphate (GGPP) and farnesylpyrophosphate, as well as cholesterol. It has been reported that treatment with 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor ameliorates glomerular injury in several experimental models of progressive glomerular disease. However, the effect of HMG-CoA reductase inhibitor on mesangial cell function has not been fully understood. This investigation was performed to elucidate the role of a mevalonate metabolite(s) in mesangial cell proliferation and extracellular matrix accumulation. METHODS: Cycling or quiescent human mesangial cells were incubated in RPMI 1640 containing 10% heat-inactivated fetal calf serum (FCS) in the absence or presence of pravastatin, an inhibitor of HMG-CoA reductase, and mevalonate metabolites. Type IV collagen secretion, mRNA expression, and [3H]thymidine incorporation were measured. Cell cycle phases were monitored by flow cytometry. RESULTS: Pravastatin inhibited FCS-stimulated type IV collagen secretion (IC50 = 210 microM) and mRNA expression. Pravastatin also inhibited FCS-stimulated [3H]thymidine incorporation (IC50 = 430 microM). Analysis with flow cytometry revealed that pravastatin inhibited the G1 to S phase transition of FCS-stimulated mesangial cells. Mevalonate reversed these inhibitory effects of pravastatin completely. Among two major metabolites of mevalonate, GGPP and farnesylpyrophosphate, only GGPP reversed pravastatin-induced inhibition of type IV collagen secretion, DNA synthesis, and the G1 to S phase progression. CONCLUSIONS: These results suggest that GGPP plays critical roles for the type IV collagen secretion and G1 to S phase transition in FCS-stimulated human mesangial cells.

Animals↗

PubMed1999

Effect of pravastatin on type IV collagen secretion and mesangial cell proliferation.

BACKGROUND: The mevalonate pathway is important for the biosynthesis of isoprenoids such as geranylgeranylpyrophosphate (GGPP) and farnesylpyrophosphate (FPP) as well as cholesterol. It has been reported that treatment with 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor ameliorates glomerular injury in several experimental models of progressive glomerular disease. The present investigation was performed to elucidate the role of mevalonate metabolites in mesangial cell proliferation and extracellular matrix accumulation. METHOD: Cycling or quiescent human mesangial cells were incubated in RPMI1640 containing 10% heat-inactivated fetal calf serum (FCS) in the absence or presence of pravastatin, an inhibitor of HMG-CoA reductase, and mevalonate metabolites. Type IV collagen secretion and mRNA expression, [3H]-thymidine incorporation was measured. Cell cycle phases were monitored by flow cytometry. RESULTS: Pravastatin inhibited FCS-stimulated type IV collagen secretion (IC50 = 210 microM) and mRNA expression. Pravastatin also inhibited FCS-stimulated [3H]-thymidine incorporation (IC50 = 430 microM). Analysis with flow cytometry revealed that pravastatin inhibited G1 to S phase transition of FCS-stimulated mesangial cells. Mevalonate reversed these inhibitory effects of pravastatin completely. Among two major metabolities of mevalonate, GGPP and FPP, only GGPP reversed pravastatin-induced inhibition of type IV collagen secretion, DNA synthesis and G1 to S phase progression. CONCLUSION: The present results suggest that GGPP plays a critical role in the type IV collagen secretion and G1 to S phase transition in FCS-stimulated human mesangial cells.

Cell Cycle↗

PubMed1999

A Lys644Glu substitution in fibroblast growth factor receptor 3 (FGFR3) causes dwarfism in mice by activation of STATs and ink4 cell cycle inhibitors.

Missense mutations of human fibroblast growth factor receptor 3 (FGFR3) result in several skeletal dysplasias, including hypochondroplasia, achondroplasia and thanatophoric dysplasia. To study the function of FGFR3 in bone growth and to create animal models for the FGFR3-related inherited skeletal disorders, we introduced a point mutation (Lys644Glu) into the murine FGFR3 genome using a knock-in approach. We found that the Lys644Glu mutation resulted in retarded endochondral bone growth with severity directly linked to the expression level of the mutated Fgfr3. Mice heterozygous for the mutation ( Fgfr3(TD/+) ) expressed the mutant allele at approximately 20% of the wild-type level and exhibited a mild bone dysplasia. However, when the copy number of the mutant allele increased from one (Fgfr3(TD/+) to two (Fgfr3(TD/TD), the retardation of bone growth became more severe and showed phenotypes resembling those of achondroplasia patients, characterized by a dramatically reduced proliferation of growth plate cartilage, macrocephaly and shortening of the long bones, which was most pronounced in the femur. Molecular analysis revealed that expression of the mutant receptor caused the activation of Stat1, Stat5a and Stat5b, and the up-regulation of p16, p18 and p19 cell cycle inhibitors, leading to dramatic expansion of the resting zone of chondrocytes at the expense of the proliferating chondrocytes. The mutant growth plates consequently were in a less active state and generated fewer maturing and hypertrophic chondrocytes. These data provide direct genetic evidence that the point mutations in FGFR3 cause human skeletal dysplasias and uncover a mechanism through which the FGFR3 signals regulate bone growth by modulating expression of Stats and ink4 cell cycle inhibitors.

Amino Acid Substitution↗

PubMed1999

A rare case of sarcoidosis with bilateral leg lymphedema as an initial symptom.

A 55-year-old man was admitted to our hospital because of bilateral leg lymphedema. He also showed subcutaneous nodules and CT scan disclosed multiple enlarged lymph nodes at thoracic, abdominal, and inguinal areas. Biopsy of the inguinal lymph node and the subcutaneous nodule revealed noncaseating epithelioid cell granuloma, a finding consistent with sarcoidosis. Lymphedema was attributed to the blockade of lymph flow by the systemic lymph node involvement of the disease. Within 1 week after the initiation of steroid therapy, his leg edema disappeared. Lymphedema could be the initial symptom of systemic sarcoidosis.

Diagnosis, Differential↗

PubMed1999

An unusual case of epithelial-myoepithelial carcinoma of the liver.

The authors present an unusual case of an epithelial-myoepithelial carcinoma of the liver in a 67-year-old man who was admitted for resection of a gastric adenocarcinoma. At operation, a 3 x 3 cm mass in the right liver lobe was also removed. This mass consisted of duct-like structures with dual differentiation. The inner layer was composed of an epithelial lining, and the outer layer consisted of clear cells, all unrelated to the moderately well-differentiated gastric adenocarcinoma. The clear cells were positive for S-100 and alpha-smooth muscle actin, suggesting myoepithelial origin. The mass was considered to be low-grade epithelial-myoepithelial carcinoma. However, the patient had a history of an oral nodule present since childhood, resected 10 years previously. These slides were reviewed and revealed a mixture of clear cells and basal cells with squamous differentiation. In addition, there were duct-like structures with the two-layer pattern found in the liver tumor. This tumor had numerous mitotic figures and showed perineural invasion, suggesting a high grade of malignancy. These findings led to an interpretation of the oral tumor as also being epithelial-myoepithelial carcinoma, which had remained as "benign" for more than 50 years and subsequently underwent malignant transformation. During this long period, liver metastases may have occurred and remained low-grade. Alternatively, the liver and oral tumors may have arisen separately in the foregut during embryologic development, remaining low-grade until malignant transformation occurred.

Actins↗

PubMed1999

Histopathological changes of the eustachian tube cartilage and the tensor veli palatini muscle with aging.

OBJECTIVES: The eustachian tube (ET) and the tensor veli palatini muscle (TVPM) are thought to play an important role in ventilatory function. Calcification of the ET cartilage and the replacement of TVPM by fat tissue are often observed histologically in elderly patients. To our knowledge, however, there are no quantitative studies of these pathological findings in relation to age. STUDY DESIGN: The calcification of the ET cartilage and the atrophy of the TVPM in 36 normal human temporal bones obtained from 36 individuals with ages ranging from 2 days to 88 years were investigated. METHODS: The number of calcified chondrocytes in the midportion of the ET cartilage was quantified as the average number of cells per square millimeter. Atrophy of the TVPM was evaluated at the midportion of the site where the TVPM is attached to the tip of lateral lamina of ET cartilage. A grade of 0, 1, 2, 3, or 4 was assessed for each section, which indicated approximately 0% to 5%, 5% to 30%, 30% to 70%, 70% to 95%, or 95% to 100% of the TVPM replacement by fat tissue, respectively. RESULTS: A statistically significant correlation was found between the number of the calcified cells and aging (P < .001). A statistically significant correlation was also found between the degree of the atrophy of TVPM and aging (P < .001). CONCLUSIONS: The calcification of the ET cartilage and the atrophy of the TVPM are closely associated with aging. Therefore, it is suggested that these two findings may be a predisposing factor for ET dysfunction in elderly adults.

Adolescent↗

PubMed1999

Postnatal growth failure, short life span, and early onset of cellular senescence and subsequent immortalization in mice lacking the xeroderma pigmentosum group G gene.

The xeroderma pigmentosum group G (XP-G) gene (XPG) encodes a structure-specific DNA endonuclease that functions in nucleotide excision repair (NER). XP-G patients show various symptoms, ranging from mild cutaneous abnormalities to severe dermatological impairments. In some cases, patients exhibit growth failure and life-shortening and neurological dysfunctions, which are characteristics of Cockayne syndrome (CS). The known XPG protein function as the 3' nuclease in NER, however, cannot explain the development of CS in certain XP-G patients. To gain an insight into the functions of the XPG protein, we have generated and examined mice lacking xpg (the mouse counterpart of the human XPG gene) alleles. The xpg-deficient mice exhibited postnatal growth failure and underwent premature death. Since XPA-deficient mice, which are totally defective in NER, do not show such symptoms, our data indicate that XPG performs an additional function(s) besides its role in NER. Our in vitro studies showed that primary embryonic fibroblasts isolated from the xpg-deficient mice underwent premature senescence and exhibited the early onset of immortalization and accumulation of p53.

Animals↗

PubMed1999

Arginine vasopressin inhibits fluid secretion in guinea pig pancreatic duct cells.

The effects of arginine vasopressin (AVP) on pancreatic ductal secretion were studied in guinea pigs. In the isolated vascularly perfused pancreas, AVP reduced secretin-stimulated fluid secretion and increased the vascular resistance when the perfusion rate was held constant. In the isolated interlobular duct segments, AVP inhibited secretin-stimulated fluid secretion, indicating the direct inhibitory action of AVP on the duct cells. AVP affected neither the basal nor the secretin-induced cAMP productions, suggesting that AVP inhibits the fluid secretion at a point distal to the production of cAMP. AVP increased intracellular Ca(2+) concentration ([Ca(2+)](i)) in the absence of extracellular Ca(2+). When [Ca(2+)](i) was elevated by the application of thapsigargin, AVP caused a rapid decrease in [Ca(2+)](i). AVP seems to activate both Ca(2+) release from intracellular stores and Ca(2+) efflux across the plasma membrane, but its relation to the inhibition of fluid secretion remains to be clarified. It is concluded that AVP directly inhibits secretin-stimulated ductal fluid secretion in the guinea pig pancreas.

Animals↗

PubMed1999

Inflammatory response to chronic otitis media in DiGeorge syndrome: a case study using immunohistochemistry on archival temporal bone sections.

Immunohistochemical analyses were conducted on archival celloidin-embedded human temporal bone sections from an 8-month-old boy with chronic otitis media and DiGeorge syndrome. We employed antigen retrieval methods with saturated sodium hydroxide-methanol solution, microwave incubation, and proteolytic treatment to demonstrate the distribution of T-lymphocytes, B-lymphocytes, macrophages, and intercellular adhesion molecule 1 (ICAM-1) expression in the middle ear. B-lymphocytes and macrophages were observed predominantly within the middle ear mucosa. T-lymphocytes were rare. Further, ICAM-1 was expressed in the vascular endothelium of the lamina propria, as well as infiltrating mononuclear cells. This suggests that the expression of ICAM-1 can be induced in the middle ear with otitis media, even if T-lymphocytes are depressed in a cell-mediated immunodeficiency disorder such as DiGeorge syndrome.

Antibodies, Monoclonal↗

PubMed1999

Distribution of psammoma bodies in the internal auditory canal and its extended areas in the human temporal bone.

The internal auditory canal (IAC) and its extended areas of 27 normal human temporal bone specimens were investigated histologically for the distribution of psammoma bodies. A total of 145 +/- 25 (mean +/- SE) psammoma bodies were counted in series of every tenth 30-microm-thick section. Psammoma bodies were observed in the IAC and around the labyrinthine portion of the facial nerve (FN), the geniculate ganglion of the FN, and the posterior ampullary nerve in the singular canal. The number of psammoma bodies increases with age. We believe that psammoma bodies are a normal finding of aging in the IAC. The compression of the FN by psammoma bodies in the labyrinthine portion of the facial canal and the distribution of numerous psammoma bodies surrounding the posterior ampullary nerve in the narrow singular canal raise the questions of the involvement of psammoma bodies in the FN and in vestibular dysfunction and the presence of psammoma bodies in the subarachnoid space.

Adolescent↗