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Biomedical subjects

M Kitagawa

Publications and source records attributed to M Kitagawa.

At least 343 records · Page 19Linked to original sources

In vivo antimelanoma effects of 4-S-cysteaminylphenol, a newly synthesized therapeutic agent specific to melanoma.

Antimelanoma effects of 4-S-cysteaminylphenol (4-S-CAP), which is a newly synthesized melanin precursor, as a chemotherapeutic agent specific to malignant melanoma were determined in an in vivo system using mouse B16 melanoma. The intraperitoneal injection of 4-S-CAP induced a slight delay in the growth period of subcutaneous melanoma of C57BL/6 mice. Survival times of mice after treatment with 4-S-CAP were a little longer than those of control mice (P < 0.05), although all mice died from the local growth of tumours. The viable cell ratio of in vivo subcutaneous tumour cells reduced to 52.8% within 24 h after treatment with 4-S-CAP, but the ratio had recovered to the control level 72 h after treatment (> 90%). Similarly, the proliferating-cell-nuclear-antigen-positive cell ratio of melanotic melanoma had reduced 24 h after treatment and recovered within 72 h after treatment, while 4-S-CAP had no effect on amelanotic tumours. The formation of lung colonies by intravenous inoculation of malignant melanoma cells was compared between mice with intraperitoneal injection of 4-S-CAP and phosphate-buffered saline only. The 4-S-CAP-treated mice had significantly fewer lung colonies compared with the control mice (P < 0.01). The results indicate that the agent, 4-S-CAP, would have a therapeutic effect on malignant melanoma for a short time in vivo and therefore the agent can be effective against a small number of tumour cells, such as lung colonies, although it had little effect on the local tumours.

Animals↗

Longitudinal changes of plasma pancreatic enzymes and hormones in experimental pancreatolithiasis in dogs.

Plasma pancreatic enzymes and hormones were longitudinally observed after producing partial obstruction of the major pancreatic duct in dogs to study an initial state of chronic pancreatitis or pancreatolithiasis. Fasting plasma immunoreactive cationic trypsin was elevated during the first six months and then decreased in a subgroup with pancreatic calculi, marked fibrosis, or duct dilatation when compared with the corresponding opposite at the end of the 12-month period. Similar but less prominent changes were found in fasting plasma immunoreactive pancreatic polypeptide (IRPP). Plasma amylase, glucose, or immunoreactive insulin or glucagon (IRG) show no significant variation. Plasma IRG and IRPP responses to intravenous insulin were reduced in the subgroups with marked pancreatic changes towards the end of the 12-month period. These results suggest that plasma pancreatic enzymes and hormones remain elevated as long as pancreatic damage is mild and then start to decline as the damage progresses in chronic pancreatitis or pancreatolithiasis.

Amylases↗

Proliferative activity of primary cutaneous melanocytic tumours.

The expression of proliferating cell nuclear antigen (PCNA) was examined in formalin-fixed paraffin-embedded tissue sections from 41 lesions (27 melanocytic nevi, 3 atypical nevi and 11 malignant melanomas) to determine the proliferative activity of primary cutaneous melanocytic tumours. Most of the malignant melanomas had more than 7% PCNA-positive cells (9.2 +/- 0.5%), while the melanocytic nevi manifested less than 1% PCNA-positive cells (0.4 +/- 0.1%). Atypical nevi exhibited an intermediate, but still significantly lower, labelling ratio when compared with malignant melanomas (0.8 +/- 0.2%). The proliferative activity of the lesions was compared between portions at different depths in the skin (epidermal, upper dermal and lower dermal location). In cases of malignant melanoma, the proliferative activity was higher in the deeper portion of dermis whereas PCNA-positive cells in melanocytic nevi were located in the upper dermis predominantly. Thus the PCNA labelling ratio of malignant melanoma and/or melanocytic nevus cells located in the epidermodermal junction was not necessarily higher than that of malignant melanoma and/or melanocytic nevus cells in the dermis. These results indicate that staining with PCNA would be very useful in the differentiation of malignant melanoma from melanocytic nevi manifesting cellular and/or structural atypia by virtue of a significant difference in the proportion of PCNA-positive cells. Although malignant melanomas have higher proliferative activity than melanocytic nevi in the deeper dermis, junctional activity in melanocytic tumours does not indicate cell proliferation.

Adolescent↗

Serum pancreatic stone protein in pancreatic diseases.

Serum pancreatic stone protein (PSP) was determined in sera of pancreatic and nonpancreatic diseases using enzyme immunoassay specific to human PSP to study the diagnostic and pathophysiological significance of PSP. Serum PSP in acute pancreatitis (mean +/- SD = 1075.4 +/- 2849.1 ng/mL, n = 33) was significantly higher than that in controls (78.6 +/- 31.8 ng/mL, n = 37, p < 0.01), chronic pancreatitis (156.8 +/- 82.8 ng/mL, n = 32, p < 0.05), and pancreatic cancer (148.468.8 ng/mL, n = 26, p < 0.05). No significant difference was found between noncalcified and calcified chronic pancreatitis. Serum PSP levels were significantly higher in chronic renal failure under hemodialysis (1796.0 +/- 1492.9 ng/mL) than in other diseases such as peptic ulcer, liver cirrhosis, gallstone, and diabetes mellitus. Low but significant correlation was obtained between serum PSP and serum immunoreactive trypsin (r = 0.22, p < 0.05). Increased serum PSP levels in acute pancreatitis and chronic renal failure suggest that serum PSP levels reflect reflex from pancreatic secretion, release from damaged pancreatic acinar cells, or retention in circulation, and can be useful for diagnosis of acute pancreatitis, but not chronic calcified pancreatitis.

Acute Disease↗

Expression of the proliferating cell nuclear antigen in bone marrow cells from patients with myelodysplastic syndromes and aplastic anemia.

To determine the proliferative activity of the hematopoietic cells under nonneoplastic and/or neoplastic conditions, the expression of a cell cycle-related antigen, the proliferating cell nuclear antigen (PCNA), was examined in the bone marrow trephines of 79 individuals, 12 of whom had no hematologic disorder, 32 of whom had a diagnosis of myelodysplastic syndromes (MDSs), 20 of whom suffered from aplastic anemia, and 15 of whom had a diagnosis of acute myeloid leukemia. Most of the patients with MDS had more than 15% PCNA-positive cells (23.5% +/- 1.5%) while patients with no hematologic disorder showed fewer than 15% PCNA-positive cells (11.7% +/- 0.7%). The overall ratio of the PCNA-positive cell fraction in the bone marrow was considered of prognostic value for predicting transition into overt leukemia from MDS. Aplastic anemia cases usually exhibited hypocellular bone marrow and an infrequent labeling with the anti-PCNA antibody (3.3% +/- 0.5%). However, a few aplastic anemia cases showed hypercellular bone marrow and a significantly high PCNA-positive cell ratio (32.0% +/- 4.4%). In the bone marrow of acute myeloid leukemia patients more than 20% of total nucleated cells were positive for PCNA (30.0% +/- 2.2%). The results suggest that the expression of PCNA is associated with the regulation of bone marrow cell proliferation and the bone marrow cellularity, and that these findings would serve as an early indicator of evolution of overt leukemia in MDS and also would be useful in distinguishing MDS cases from aplastic anemia cases when the bone marrow is hypocellular or normocellular.

Acute Disease↗

Analysis of prognostic factors in patients with resected peripheral T1 adenocarcinoma of the lung.

Prognostic factors in patients with surgically-treated peripheral T1 (< or = 3 cm in greatest diameter) adenocarcinoma of the lung were analyzed in 45 cases. Statistical difference in survival was observed between stages I + II and III + IV (p < 0.05). However, neither sex, age, location of tumor, histological subtype, histological grade, tumor ploidy, nor presence of central fibrosis was of prognostic determinance. Our results suggest that only clinical stage is of prognostic importance in surgically-treated peripheral T1 adenocarcinoma of the lung.

Adenocarcinoma↗

Further study of nebulisation chemotherapy, a new chemotherapeutic method in the treatment of lung carcinomas: fundamental and clinical.

Nebulisation chemotherapy, a chemotherapeutic method for the treatment of lung cancer that involves the administration of anticancer agents through the inhalation of nebulised aerosols, has been found to be highly effective (Tatsumura et al., 1983a,b). We confirmed that 5-FU administered by this method accumulates in the trachea, bronchi and regional lymph nodes of patients treated before surgery, along with 5-FU metabolites, FUR and FUdR, indicating that 5-FU is directly incorporated and metabolised in the respiratory tract. Parallel result were obtained using mongrel dogs. The 5-FU levels in other organs, such as the heart and liver, were found to be extremely low. Only a trace of 5-FU was found in the serum of both the patients and the dogs. We further investigated the anti-tumour effect of this therapy in ten selected patients and observed a satisfactory anti-tumour response of 60.0%. These results, along with our previous finding that the retention time of isotope tracers inhaled as aerosol is considerably longer in tumour tissues than in normal parts (Tatsumura et al., 1983a) explain the high antitumour action of this therapy and the absence of adverse effects of administered 5-FU.

Adenocarcinoma↗

Effect of a new synthetic trypsin inhibitor on taurocholate-induced acute pancreatitis in rats.

The effect of a novel synthetic trypsin inhibitor, 4-sulfamoylphenyl 4-guanidinobenzoate methanesulfonate (ONO-3307), on severe acute pancreatitis was studied by changing its timing, frequency, and dose in trypsin-taurocholate-induced acute experimental pancreatitis in rats. Rats were divided into four groups according to difference of ONO-3307 administration: group A, 2 mg/0.5 ml of ONO-3307 s.c. 1 h before and after induction of pancreatitis; group B, 2 mg/0.5 ml s.c. 1 and 3 h after; group C, 4 mg/1 ml s.c. 1 h before; group D, 4 mg/1 ml s.c. 1 h after. The survival rate at 24 h was significantly improved in group A (75% in A vs. 17% in control; p < 0.01) and in group B (57 vs. 29%; p < 0.05), but not in group C or D. Amylase and immunoreactive trypsin in serum and ascites of the treated were significantly lower than those of controls in both groups A and B. The survival rates were improved dose dependently when ONO-3307 was administered 1 h before and after induction of pancreatitis. ONO-3307 showed favorable effects on the initial stage of severe acute pancreatitis when given in divided doses to maintain the effective serum levels.

Acute Disease↗

Lung carcinoma mimicking malignant lymphoma: report of three cases.

Three cases of lung carcinomas with unusual histologic appearances that have received little or no comment in the literature are presented. They were initially confused with malignant lymphoma because of a diffuse proliferation of relatively monotonous cells simulating large-cell immunoblastic lymphoma. In each case, the possibility of malignant lymphoma was excluded with confidence after the immunohistochemical study (leucocyte common antigen negative and cytokeratins positive), although with conventional microscopy several foci of cohesive groups of tumor cells were observed. The tumors were ranked at the clinical stage II or III when they were initially discovered, but all patients died of disease within 1 year. The present three tumors show an aggressive behavior and could be classified into a peculiar variant of 'large cell' carcinoma. It is necessary for surgical pathologists to have an idea of these variants of lung carcinoma in order to avoid erroneous diagnosis.

Adult↗

The effect of somatostatin analogue octreotide on amylase secretion from mouse pancreatic acini.

To clarify whether somatostatin has an inhibitory effect on pancreatic acinar cells, we studied the effect of a long-acting analogue of somatostatin, octreotide, on amylase secretion from isolated mouse pancreatic acini. Octreotide (100 nM) had no inhibitory effects on amylase secretion stimulated by secretin or vasoactive intestinal polypeptide (VIP), while reducing the increase of cyclic adenosine 3',5'-monophosphate (cAMP). On the other hand, octreotide inhibited synergistic amylase secretion induced by secretin or VIP in combination with cholecystokinin (CCK). Octreotide also reduced synergistic amylase secretion by secretin or VIP in combination with calcium ionophore A23187. CCK and A23187 did not alter the increase of cAMP induced by secretin and the inhibitory effect of octreotide on cAMP production. Octreotide did not significantly inhibit amylase secretion stimulated by dibutyryl cAMP (dbcAMP) alone, but reduced synergistic amylase secretion by dbcAMP+A23187. Results obtained above reveal that octreotide has a direct inhibitory effect on amylase secretion from mouse pancreatic acini and probably affects stimulus secretion coupling at a point distal to the production of cAMP, besides inhibiting adenylate cyclase.

Amylases↗

Absorption mechanism of 1,3-bis(2-ethoxycarbonylchromon-5-yloxy)-2-((S)-lysyloxy )propane dihydrochloride (N-556), a prodrug for the oral delivery of disodium cromoglycate.

To clarify the absorption mechanism of 1,3-bis(2-ethoxycarbonylchromon-5-yloxy)-2-((S)-lysyloxy+ ++)propane dihydrochloride (N-556), a prodrug for the oral delivery of disodium cromoglycate (DSCG), a study was made using rats. N-556 gave the highest plasma level of DSCG following its injection into the loop at the upper part of the small intestine. N-556 was stable in acidic washings of gastric contents, but rapidly hydrolyzed to M1 with twin ethyl residues on DSCG in the washings of the small intestinal contents. N-556 and M1 were hydrolyzed to DSCG via M2 having a mono ethyl residue in the homogenate of the small intestinal mucosa. The oral absorption of M1 following its administration in 50% (v/v) propylene glycol solution was essentially the same as that of N-556. That of M1 administered in aqueous suspension was low. After the oral administration of N-556, a small amount of M2 and a trace of M3 having L-lysyl residue were detected in the portal plasma, but no hydrolytic intermediate except DSCG could be found in the general plasma. The major absorption mechanism of N-556 may thus be concluded as follows: N-556 given orally is transferred to the small intestine in essentially intact form. N-556 is then rapidly diffused to an aqueous layer on the surface of the mucosal membrane and hydrolyzed to M1. The resultant M1 is transported to the mucosal membrane and hydrolyzed to DSCG via M2. DSCG generated in the mucosal membrane is used for general circulation through the portal blood and liver.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Abscessing bronchioloectasia with elements of plasma cell granuloma.

A 79-year-old male was admitted to the hospital with the complaint of bloody sputum. Chest X-ray revealed an abnormal shadow in the right upper lobe. Macroscopically, the lesion measured about 3.5 x 2.5 x 2.0 cm with a central cavity containing pus. Histologically, the lesion was composed of interlacing fibroblastic proliferation with abundant plasma cell infiltration and central cavitation. The inner surface of the cavity wall was partially covered by bronchial epithelial cells; there was no cartilage found, suggesting that the lesion had developed from chronic inflammatory processes in relation to ectatic bronchioles. Since the pathogenesis of plasma cell granuloma (PCG) has not been well established, it is probable that this case represents one stage in the development of classic PCG.

Aged↗

Small, polypoid-appearing carcinoid tumors of the rectum: clinicopathologic study of 16 cases and effectiveness of endoscopic treatment.

Fifteen cases of small-size rectal carcinoid tumors (RCTs) were discovered among a total of 21,522 healthy teachers who received proctosigmoidoscopy. Adding another case seen in the outpatients, a total of 16 RCTs were clinicopathologically studied. The average age of the patients was 48.8 yr, and the incidence was predominantly among males. Prior to endoscopy, digital examination of the rectum revealed a palpable firm nodule in 13 patients. On endoscopy, RCTs were generally round, yellow-discolored polyps with a size less than 13 mm in diameter, covered by a normal-appearing mucosa. An erythematous change or depression was seen in three tumors. Histologically, they showed pure insular, trabecular, or mixed structures, and tumor cells were confined to the mucosa and/or submucosa in all cases. Immunohistochemically, RCTs never failed to show focal or diffuse positivities for chromogranin A and/or neuron-specific enolase. Pancreatic polypeptide was immunostained in 14 tumors to a varying degree. The tumors having been safely treated by endoscopic polypectomy and/or surgical excision, all of the patients are alive and clinically free of disease during the average observation period of 79 months.

Carcinoid Tumor↗

[A case of idiopathic thrombocytopenic purpura associated with eosinophilic pneumonia with unusual shadows].

A 31-year-old woman who had been diagnosed as having idiopathic thrombocytopenic purpura at her first delivery (July, 1991) was admitted to our hospital on 17 July, 1992 for dry cough and abnormal chest shadow. Chest CT showed a hemisphere-like shadow in the left upper lung field. The TBLB specimen showed a mild eosinophilic pneumonia. When the patient was observed without medications, a ring-like shadow appeared newly in the right middle field and the both shadows became gradually wider and lighter. Cases of eosinophilic pneumonia showing such shadows are considered to be very rare and interesting.

Adult↗

[A case of eosinophilic pneumonia due to tolfenamic acid].

We report a case of pneumonitis induced by tolfenamic acid. A 23-year-old woman was admitted to our hospital because of cough and fever. She had been treated with tolfenamic acid and other medications for lumbago. Nine days after the treatment, she developed erythema, fever, cough and dyspnea. Her chest X-ray revealed multiple patchy and micronodular shadows in both lung fields. Bronchoalveolar lavage fluid (BALF) showed increased total cells, lymphocytes, eosinophils and CD4/CD8 ratio. Microscopic examination of transbronchial lung biopsy (TBLB) specimens showed infiltration of mononuclear cells and eosinophils into the alveolar wall and the interstitium. After discontinuation of all drugs, her complaints, laboratory data and chest X-ray findings markedly improved. The lymphocyte stimulation test (LST) and challenge test for tolfenamic acid were positive. Based on these findings, we diagnosed this case as pneumonitis (eosinophilic pneumonia) due to tolfenamic acid. To our knowledge, there has been no reported case of pneumonitis due to this drug in Japan.

Adult↗