Biomedical subjects

M Kitagawa

Publications and source records attributed to M Kitagawa.

At least 217 records · Page 12Linked to original sources

PubMed1997

Geranylgeranylated rho small GTPase(s) are essential for the degradation of p27Kip1 and facilitate the progression from G1 to S phase in growth-stimulated rat FRTL-5 cells.

Cyclin-dependent kinase (Cdk) enzymes are activated for entry into the S phase of the cell cycle. Elimination of Cdk inhibitor protein p27Kip1 during the G1 to S phase is required for the activation process. An inhibitor of 3-hydroxy-3-methylglutaryl-CoA reductase prevents its elimination and leads to G1 arrest. Mevalonate and its metabolite, geranylgeranyl pyrophosphate, but not farnesyl pyrophosphate, restore the inhibitory effect of pravastatin on the degradation of p27 and allow Cdk2 activation. By the addition of geranylgeranyl pyrophosphate, Rho small GTPase(s) are geranylgeranylated and translocated to membranes during G1/S progression. The restoring effect of geranylgeranyl pyrophosphate is abolished with botulinum C3 exoenzyme, which specifically inactivates Rho. These results indicate (i) among mevalonate metabolites, geranylgeranyl pyrophosphate is absolutely required for the elimination of p27 followed by Cdk2 activation; (ii) geranylgeranylated Rho small GTPase(s) promote the degradation of p27 during G1/S transition in FRTL-5 cells.

Animals↗

PubMed1997

Leiomyosarcoma of the colon presenting as acute suppurative peritonitis.

A surgical case of leiomyosarcoma arising from the ascending colon, presenting as acute suppurative peritonitis, is herein described. A 70-year-old woman complaining of lower abdominal pain presented to our clinic on October 12, 1994. She was admitted with a tentative diagnosis of peritonitis. At emergency laparatomy, purulent intraabdominal fluid was present, and a fist-sized mass was seen in the ascending colon just proximal to the hepatic flexure. A right hemicolectomy was thus performed based on a diagnosis of perforating colon cancer. The histologic findings were consistent with leiomyosarcoma with abscess formation in and around the tumor. Five mitotic figures per field were observed at 10x magnification. Immunohistochemical studies revealed immunoreactivity for alpha-smooth muscle antigen (alpha-SMA), vimentin, and desmin. After reviewing the clinicopathologic characteristics of colon leiomyosarcoma as described in 78 Japanese cases and 70 cases from the foreign literature, we thus propose that colon leiomyosarcoma frequently arises from the transverse colon. In addition, our case also represents the only reported case in Japan in which an adult patient underwent a successful operation for perforated leiomyosarcoma of the colon.

Acute Disease↗

PubMed1997

Overexpression of tumor necrosis factor (TNF)-alpha and interferon (IFN)-gamma by bone marrow cells from patients with myelodysplastic syndromes.

To clarify whether regulatory cytokines inhibit hematopoiesis in patients with myelodysplastic syndromes (MDS), malignancies characterized by the formation of cytopenias despite the presence of cellular bone marrow, expression of TNF-alpha and IFN-gamma by bone marrow cells was investigated using specific reverse transcriptase-polymerase chain reaction assays. An enhanced expression of the mRNA for TNF-alpha was observed in most of the samples from MDS patients (11/14, 79%), whereas no enhancement was observed in bone marrow samples from AML (0/6), CML (0/2) or control cases (0/8). The expression of IFN-gamma was also enhanced in some of MDS cases (5/12, 42%) while AML (0/5), CML (0/2) and control cases (0/6) showed very low levels of IFN-gamma mRNA expression. Immunohistochemical examination confirmed the scattered presence of TNF-alpha or IFN-gamma producing cells in the bone marrow of MDS patients. The majority of these cells were CD68-positive macrophage lineage cells. These results suggested that disruption of hematopoiesis in MDS might be caused by enhanced production of inhibitory regulatory cytokines especially TNF-alpha and occasionally IFN-gamma by bone marrow macrophages.

Adult↗

PubMed1997

Limiting dilution analysis of T-cell progenitors in the bone marrow of thymic lymphoma-susceptible B10 and -resistant C3H mice after fractionated whole-body X-irradiation.

Earlier studies from this laboratory using Thy 1 congenic B10 strain mice suggested that a depletion of T cell progenitors (pre T cells) in the bone marrow in addition to the destruction of the thymus after fractionated whole body X-irradiation (IR) are the two main critical factors that cause differentiation arrest of initially repopulating intrathymic radio-resistant T cell progenitors, which then lead to the appearance of preneoplastic, prelymphoma cells, and eventually to highly neoplastic thymic lymphomas under the influence of the thymic environment. In order to explore the significance of the depletion (or reduction) of T cell progenitors in the bone marrow during pathogenesis of radiation-induced thymic lymphomas, we compared the pool size of pre T cells in the bone marrow and the spleens as well as the profiles of the regenerating thymocyte populations between thymic lymphoma induction-susceptible B10 and -resistant C3H strain mice following irradiation. The results indicated that irradiation severely depleted the pre T cells in the bone marrow and the spleens of both lymphoma induction-susceptible and -resistant mice. They also showed that in C3H mice the differentiation and maturation of intrathymic T cell progenitors which initially repopulated the depleted thymus seemed to proceed normally in spite of the poor cellularity, while this process was greatly suppressed in B10 mice. These data indicate that a depletion of pre T cells in the bone marrow combined with atrophy of the thymus in the irradiated mice is necessary, but not sufficient for development of thymic lymphoma. Implication of these findings on the possible mechanism of radiation-induced thymic lymphomagenesis is discussed.

Animals↗

PubMed1997

Consumption of cow milk and egg by lactating women and the presence of beta-lactoglobulin and ovalbumin in breast milk.

beta-Lactoglobulin and ovalbumin in mature human milk in healthy lactating Japanese women (n = 24) were determined by using an enzyme-linked immunosorbent assay. Subjects consumed > or = +200 mL cow milk/d for 1 wk before the sampling day and exactly 200 mL cow milk on the morning of the sampling day. beta-Lactoglobulin was detected (> 0.1 microgram/L) in breast milk in 15 of the 24 subjects (62.5%), with a maximum concentration of 16.5 micrograms/L. Ovalbumin was detected in only two subjects (8.3%) after the subjects followed their usual diet. beta-Lactoglobulin concentrations were low in the subjects whose cow milk consumption during the entire lactating period was low, even though all subjects consumed the same amount of cow milk before sampling. This result suggests that beta-lactoglobulin concentrations in breast milk are related to long-term consumption of cow milk. Amounts of food antigens in breast milk may be controlled by modifying the daily maternal diet.

Adult↗

PubMed1997

Lung cancer associated with Werner's syndrome: a case report and review of the literature.

A 52-year-old male had an abnormal shadow on a chest X-ray film. His parents were first cousins. His father, brother and two sisters had been diagnosed with Werner's syndrome. His lung lesion was diagnosed as lung cancer and right upper lobectomy was carried out. Histopathological examination of the resected specimen revealed bronchiolo-alveolar carcinoma with independent atypical adenomatous hyperplasia in the alveolar zone. The alveolar structures were those seen in aging lungs, suggesting a close relationship between Werner's syndrome and cancer development.

Adenocarcinoma, Bronchiolo-Alveolar↗

PubMed1997

Change of pancreatic enzymes, pancreatic stone protein (PSP), and plasma alpha(2)-macroglobulin-trypsin complex-like substance (MTLS) in the activation of pancreatic juice.

To characterize the activation of pancreatic zymogens (trypsinogen, chymotrypsinogen, and proelastase 1) in acute pancreatitis, we studied the activation of pancreatic juice with porcine enteropeptidase in vitro, and then enzymatic activities and the generation of pancreatic stone protein (PSP) S1 form in pancreatic juice were investigated. Further, we determined immunoreactive trypsin, immunoreactive elastase 1, PSP, and alpha(2)-macroglobulin-trypsin complex-like substance (MTLS) levels in plasma to which the activated juice was added. In the present report, we demonstrate that the plasma MTLS level reflected the activation of pancreatic trypsinogen in pancreatic juice. Further, the generation of PSP S1 form was found at an early stage of activation. Therefore, the plasma MTLS level and the generation of PSP S1 form may offer new diagnostic information on the amounts of activated proteases and subsequently on the severity of acute pancreatitis.

Animals↗

PubMed1997

Evaluating exocrine function tests for diagnosing chronic pancreatitis.

To evaluate the effectiveness of exocrine function tests in diagnosing chronic pancreatitis (CP), we compared the sensitivity and specificity of duodenal intubation with tubeless tests. While the secretin test (ST) was necessary to diagnose CP, especially in noncalcified CP, and tubeless tests demonstrated insufficient sensitivity to diagnose CP, the combination assay of tubeless tests was specific enough to diagnose severe exocrine dysfunction. Our studies found the sensitivity of secretin testing to diagnose definite CP to be 87%. In patients with probable CP, 60% had mild exocrine insufficiency and 40% had normal function. The false-positive rate of the ST results in nonpancreatic diseases, except diabetes mellitus, was 5%. The correlation between morphological changes in endoscopic retrograde pancreatography (ERP) and exocrine function evaluated by ST was 74%. In patients with calcified CP, 81% had parallel results between ERP and the ST, but in noncalcified CP, 47% had parallel results. In patients with severe or moderate exocrine insufficiency demonstrated by ST, abnormally low levels were observed in 63% by N-benzoyl-L-tyrosyl-p-aminobenzoic acid (BT-PABA) test, 61% by fecal chymotrypsin test (FCT), and 44% by pancreatic amylase (PA). In patients with normal exocrine function demonstrated by ST, abnormally low levels were observed in 28% by BT-PABA test, 28% by FCT, and 10% by PA. A combination assay of BT-PABA test, FCT, and PA improved the specificity for diagnosing CP but not the sensitivity.

4-Aminobenzoic Acid↗

PubMed1997

Eosinophilic pneumonia caused by Alternaria alternata.

We describe a patient who presented with hypoxemia and diffuse bilateral pulmonary infiltrates. The diagnosis of eosinophilic pneumonia was confirmed by bronchoalveolar lavage and transbronchial lung biopsy. The remarkable characteristic was reappearance of the symptoms on the patient's return home, suggesting the existence of etiologic agents in his house. An environmental survey of the patient's house yielded Alternaria alternata. A high titer of anti-A. alternata antibody (IgG) was detected in his serum, and the inhalation bronchoprovocation test with A. alternata antigen was positive. This case indicates that A. alternata is a probable cause of eosinophilic pneumonia.

Aged↗

PubMed1997

Activation of the STAT signaling pathway can cause expression of caspase 1 and apoptosis.

Protein tyrosine kinases activate the STAT (signal transducer and activator of transcription) signaling pathway, which can play essential roles in cell differentiation, cell cycle control, and development. However, the potential role of the STAT signaling pathway in the induction of apoptosis remains unexplored. Here we show that gamma interferon (IFN-gamma) activated STAT1 and induced apoptosis in both A431 and HeLa cells, whereas epidermal growth factor (EGF) activated STAT proteins and induced apoptosis in A431 but not in HeLa cells. EGF receptor autophosphorylation and mitogen-activated protein kinase activation in response to EGF were similar in both cell lines. The breast cancer cell line MDA-MB-468 exhibited a similar response to A431 cells, i.e., STAT activation and apoptosis correlatively resulted from EGF or IFN-gamma treatment. In addition, in a mutant A431 cell line in which STAT activation was abolished, no apoptosis was induced by either EGF or IFN-gamma. We further demonstrated that both EGF and IFN-gamma induced caspase 1 (interleukin-1beta converting enzyme [ICE]) gene expression in a STAT-dependent manner. IFN-gamma was unable to induce ICE gene expression and apoptosis in either JAK1-deficient HeLa cells (E2A4) or STAT1-deficient cells (U3A). However, ICE gene expression and apoptosis were induced by IFN-gamma in U3A cells into which STAT1 had been reintroduced. Moreover, both EGF-induced apoptosis and IFN-gamma-induced apoptosis were effectively blocked by Z-Val-Ala-Asp-fluoromethylketone (ZVAD) in all the cells tested, and studies from ICE-deficient cells indicated that ICE gene expression was necessary for IFN-gamma-induced apoptosis. We conclude that activation of the STAT signaling pathway can induce apoptosis through the induction of ICE gene expression.

Apoptosis↗

PubMed1997

US-guided left-sided biliary drainage: nine-year experience.

PURPOSE: The feasibility and safety of left-sided biliary drainage with ultrasound (US) guidance were studied prospectively. MATERIALS AND METHODS: From July 1987 to July 1996, 208 consecutive patients underwent US-guided biliary drainage; all were evaluated for left-sided drainage. Drainage procedure was begun with puncture of the hepatic duct branch of the lateral segment of the left lobe when the branch was well visualized with US; otherwise, a right-sided approach was used. When the hepatic duct branch diameter was greater than 3 mm, puncture was performed with an 18-gauge needle; smaller branches were punctured with 21-gauge needles. RESULTS: In 147 (71%) patients, the left hepatic duct branch was well visualized with US, and the branch diameter was greater than 3 mm. In these patients, left-sided drainage with use of an 18-gauge needle was successful. In 26 (12%) patients, the left hepatic duct branch diameter was less than 3 mm, and drainage was initiated with a 21-gauge needle. In six (23%) of these 26 patients, left-sided drainage was unsuccessful, but five of these patients underwent successful US-guided drainage from the right hepatic duct branch. Two patients died of septic shock within 72 hours of completed drainage. Three patients experienced severe hemobilia. CONCLUSION: US-guided left-sided biliary drainage is a highly successful and safe method when the left hepatic duct branch diameter is greater than 3 mm.

Adolescent↗

PubMed1997

Pneumonitis caused by saikokeisikankyou-tou, an herbal drug.

A 57-year-old man was admitted to our hospital because of dyspnea and abnormal shadow on chest roentgenogram. He had received two herbal drugs: Saikokeisikankyou-tou (SKT) for one month and Licium Halimifolium Mil (LHM) for two weeks. After admission, all medication was stopped and his symptoms were gradually diminished. Transbronchial lung biopsy specimens showed interstitial pneumonia. Lymphocyte stimulation test, skin test and challenge test were positive to these herbal drugs. We diagnosed him as drug-induced pneumonitis. This is the first report on pneumonitis caused by Saikokeisikankyou-tou diagnosed by lymphocyte stimulation test, skin test and challenge test.

Biopsy↗

PubMed1997

Hypothalamic pilocytic astrocytoma presenting with intratumoral and subarachnoid hemorrhage.

A 45-year-old male presented with sudden onset of severe headache. Computed tomography and magnetic resonance imaging demonstrated an irregularly enhanced suprasellar mass with intratumoral and subarachnoid hemorrhage. The mass was removed in two operations. Histological examination of the tumor revealed pilocytic astrocytoma. The relatively rich vascularity and perivascular tumor cell proliferation observed in this benign lesion were probably the causes of this extremely rare association.

Astrocytoma↗

PubMed1997

Preventive effect of whey hydrolysate formulas for mothers and infants against allergy development in infants for the first 2 years.

We studied the preventive effect against allergies in infants who and whose mothers consumed hypoallergenic formulas until 6 months after birth. Mother and infant pairs were divided into three groups, and the infants were monitored for the development of allergies for the first 2 years. In the MD group (n = 102; n = number of infants), the mothers were given a hypoallergenic formula for mothers (MOM HA), which contained hydrolyzed whey protein as the only protein source, as a substitution for cow's milk during late pregnancy and lactation. In the CD group (n = 127), the mothers were given cow's milk during the corresponding period. All infants in the MD and CD groups were exclusively breast-fed or mixed-fed with breast milk and hypoallergenic infant formula (NAN HA), which contains the same hydrolyzed protein as MOM HA. In the AF group (n = 54), the mothers consumed MOM HA and their infants were mixed-fed with breast milk and a cow's milk-based adopted infant formula during the corresponding period. In the MD group, no infants were positive to cow's milk-specific immunoglobulin E (RAST) at 4 months of age, in contrast to 6% and 3% of infants in the CD and AF groups, respectively. The infants in the MD group showed low incidence of various allergies, especially of eczema, as compared to the CD and AF groups. These results suggest that consumption of cow's milk by mothers and cow's milk-based formula feeding to infants elevate the risk of allergies in infants, and that consumption of hypoallergenic formula for pregnant and lactating women and for infants could be helpful in preventing allergy development in infants.

Dairy Products↗

PubMed1997

Long-term consumption of whey hydrolysate formula by lactating women reduces the transfer of beta-lactoglobulin into human milk.

Food antigens transferred into breast milk sometimes cause an allergic reaction in exclusively breast-fed infants. This study will show whether the intake of a whey hydrolysate formula for lactating women (MOM HA) can reduce the appearance of food antigens in breast milk. Lactating women in the MOM group (n = 12) consumed MOM HA as a substitute for cow's milk and those in the COW group (n = 13) consumed cow's milk for more than 4 months. After the ingestion of 200 mL of MOM HA and cow's milk by the women in the MOM and COW groups, respectively, the first breast milk samples were obtained and beta-lactoglobulin was measured using enzyme-linked immunosorbent assay. The number of subjects with detectable beta-lactoglobulin (> 0.1 ng/mL) in the MOM group was two (17%), which was significantly less than that in the COW group (11 subjects, 85%, p < 0.01). The level of beta-lactoglobulin was also lower in the MOM group than the COW group (p < 0.01). Subsequently, the women in the MOM group consumed cow's milk and those in the COW group consumed MOM HA for one week; then a second sampling was performed. beta-Lactoglobulin was detected in three (25%) and 8 subjects (62%) in the MOM and COW groups, respectively. The level of beta-lactoglobulin was still lower in the MOM group (p < 0.05). The consumption of whey hydrolysate formula by lactating women over a considerable time reduces the transfer of beta-lactoglobulin into their breast milk, and the low level can be maintained even after inadvertent ingestion of cow's milk.

Animals↗

PubMed1997

[Drug-induced pneumonitis associated PABRON-GOLD].

A 75-year-old man had for many years taken the commercially sold medicine PABRON-S whenever he caught a cold. He caught a cold and took the drug six days before admission. When PABRON-S was not available, he took PABRON-GOLD and experienced dyspnea the next day. A roentgenogram at another hospital revealed bilateral diffuse lung shadows. He was referred to our hospital. A thoracic CT scan showed bilateral interstitial shadows. Bronchoalveolar lavage fluid contained inflammatory cells including neutrophils and lymphocytes. Examination of a transbronchial lung biopsy specimen showed infiltration of mononuclear cells into the thick alveolar wall and interstitum. A drug lymphocyte stimulation test with PABRON-GOLD was positive. Based on these findings, we believe that this patient had drug-induced pneumonitis caused by PABRON-GOLD. He was treated with a steroid hormone and his symptoms resolved immediately, the abnormal roentgenographic shadows remained longer.

Acetaminophen↗

PubMed1997

[A case of pleural metastasis of invasive thymoma with pulmonary metastasis responding to chemotherapy with cyclophosphamide and prednisolone].

The patient, a 48-year old male, was seen with hoarseness in December 1990. A chest radiograph and chest CT scan showed an anterior mediastinal mass. Median sternotomy revealed epithelial thymoma with involved partial lung and pericardium. After surgery, he received external radiation to the mediastinum. One year later he was given another 40 Gy external radiation in the cervical and mediastinal recurrence region. In May 1994, a chest CT scan revealed an extrapleural and bilateral lung mass. Histological examination revealed recurrent epithelial thymoma in the left cervical muscle biopsy, so treatment with cyclophosphamide and prednisolone were begun. A dose of 100 mg/body/day of cyclophosphamide and a dose of 10 mg/body/day of prednisolone were administered every 2 week. Complete remission was induced with four cycles of this treatment of cyclophosphamide and prednisolone. The chemotherapy was thus continued for 20 cycles in 14 months. This chemotherapy with cyclophosphamide and prednisolone appeared to be useful and safe for recurrent thymoma at the outpatient clinic level.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1997

Clinicopathologic factors influencing the long-term prognosis following hepatic resection for large hepatocellular carcinoma more than 10 cm in diameter.

We resected 158 cases of hepatocellular carcinoma (HCC), including 20 (12.6%) cases of large HCC. These 20 cases were divided into group 1 (curative resection, n = 9) and group 2 (noncurative resection, n = 11). The clinicopathologic features and long-term survival of the cases were evaluated. In groups 1 and 2, portal vein invasion (Vp+) was noted in 44.4% and 63.3%, intrahepatic metastasis (IM+) in 77.8% and 100%, absence of a fibrous capsule (Fc-) in 55.6% and 63.6%, and stage III or IV in 77.8% and 100%, respectively. The DNA ploidy pattern was aneuploid in 44.4% of group 1 and 100% of group 2. In group 1, the 1-, 3-, and 5-year cumulative survival rates were 75%, 62.5%, and 62.5%, respectively (the longest survivor is alive after 11 years 1 month). Five cases survived more than 3 years in group 1, and all were Vp(-) and nonaneuploid. On the other hand, in group 2, the 1-year survival rate was only 33.3%; none survived more than 2 years. These results suggest that even patients with large HCC have a favorable long-term prognosis if their clinicopathologic factors are Vp(-) and nonaneuploid, and if curative resection can be performed.

Adult↗