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Biomedical subjects

S Kitamura

Publications and source records attributed to S Kitamura.

At least 91 records · Page 5Linked to original sources

[Classification and concept of mycobacterial infections].

Mycobacterial infections are consisted of three categories; tuberculosis, nontuberculous mycobacterioses, and leprosy. Tuberculosis is a systemic infectious disease involving respiratory, genitourinary and lymphatic systems caused by Mycobacterium tuberculosis complex (Mycobacterium tuberculosis, M. bovis, M. africanum, and M. microti). Extrapulmonary tuberculosis remains a significant clinical problem because symptoms and signs may be difficult to recognize and to relate to tuberculosis. Miliary tuberculosis is responsible for up to 10% of predominantly extrapulmonary cases. HIV-related miliary tuberculosis is rapidly progressive and almost always fatal without treatment. Nontuberculous mycobacteria (NTM) have been commonly implicated as opportunistic pathogens in patients with underlying disease or immunosuppression including AIDS. M. avium complex (M. avium and M. intracellulare) and M. kansashii are most common causes of nontuberculous mycobacterial diseases in humans. M. leprae is the causative agent of leprosy, an infection of the skin, mucous membranes, and peripheral nerves. This disease is rare in Japan, yet it remains a major problem in some part of the world.

Female

[Effectiveness of surgical repair of mitral regurgitation concomitant with dilated cardiomyopathy].

Dilated cardiomyopathy (DCM) is often accompanied by severe mitral regurgitation (MR) which deteriorates the clinical course. Mitral reconstruction for severe MR may improve the symptoms and prognosis. Five patients with DCM and one patient with dilated phase of hypertrophic cardiomyopathy underwent mitral reconstruction for severe MR (4 males, 2 females, mean age 50 +/- 17 years) from 1983 to 1995. Their New York Heart Association (NYHA) functional class and findings of echocardiography and cardiac catheterization were compared before and after surgery. Five patients underwent annuloplasty and one patient underwent mechanical valve replacement. There was no operative or in-hospital death. NYHA class improved from 3.2 to 1.8 (p < 0.05). The degree of MR was reduced from 3.5 to 1.2 (p < 0.05), and left ventricular end-diastolic pressure decreased from 18 +/- 7 to 13 +/- 8 mmHg (p < 0.05). Left ventricular fractional shortening, ejection fraction and cardiac index (2.4 +/- 0.4 to 2.7 +/- 1.1 l/min/m2) did not change significantly. Two patients died within one year due to exacerbation of congestive heart failure (2.5 month later) or sudden death (6 months later). Three patients died at 21 months, 5 and 8 years after the operation (renal insufficiency, heart failure, sudden death, respectively). Mitral reconstruction improved the symptoms in patients with DCM and severe MR in the short term. However, 5 of 6 patients died in the intermediate or long-term. Mitral reconstruction may be a therapeutic option for early outcome in patients with refractory congestive heart failure due to DCM and severe MR.

Adult

[Perinatal and perianesthetic management of the sacrococcygeal teratoma in a neonate].

We report perinatal and perianesthetic management of a female infant with sacrococcygeal teratoma who underwent fetal bladder puncture and postnatal tumor resection. At 33 weeks' gestation, fetal ultrasonography revealed an intrapelvic mass, oligohydramnios and the dilatation of the bladder. At 34 weeks' gestation, bladder puncture was performed in utero to relieve urinary obstruction by the mass. And it served to reserve the renal function but caused remarkable ascites at birth due to urine leakage to the peritoneum through the puncture site. After the delivery by cesarean section, the patient underwent the tumor extirpation at 2 days of life. The operation and anesthesia proceeded uneventfully. In previous reports, several mortalities due to exsanguinating hemorrhage during surgery have been reported. In addition, sacrococcygeal teratoma is occasionally accompanied by coagulopathy and high output cardiac failure caused by arteriovenous fistulae. Therefore it is important for good patient outcomes to evaluate preoperatively the risks mentioned above.

Anesthesia, General

Anti-inflammatory and bronchodilator properties of KF19514, a phosphodiesterase 4 and 1 inhibitor.

We investigated the effects of KF19514 (5-phenyl-3-(3-pyridyl)methyl-3H-imidazo[4,5-c][1,8]naphthyridin-4 (5H)-one) on bronchoconstriction and allergic inflammation in guinea pigs and on tumor necrosis factor-alpha production in mice. KF19514 inhibited phosphodiesterase 4 (IC50 = 0.40 microM) and phosphodiesterase 1 (IC50 = 0.27 microM) derived from canine tracheal smooth muscles. KF19514 relaxed contracted tracheal smooth muscle and had a potent inhibitory effect on antigen-induced bronchoconstriction (EC50 = 0.058 microM) in vitro. Intravenous administration of KF19514 inhibited histamine-induced bronchoconstriction (ID50 = 2.8 microg/kg i.v.). Moreover, oral administration of KF19514 inhibited anaphylactic bronchoconstriction (ID50 = 0.2 mg/kg p.o.), and eosinophil infiltration in airway stimulated with platelet-activating factor (PAF) or antigen. KF19514 also produced a significant inhibition of tumor necrosis factor-alpha production in mice (ID50 = 0.023 mg/kg p.o.). Finally, KF19514 completely inhibited antigen-induced hyperreactivity at 0.1 mg/kg p.o. These results demonstrate that KF19514 may have efficacy in the treatment of asthma.

Anaphylaxis

Induction of heparin binding epidermal growth factor-like growth factor and amphiregulin mRNAs by gastrin in the rat stomach.

The present study was designed to investigate whether heparin-binding epidermal growth factor-like growth factor and its related peptides are expressed in response to gastrin in rat stomach. Rat gastrin-17I (2.5 nmol/kg/hour) or gastrin-17I plus gastrin receptor antagonist, L-740,093 (2.0 mg/kg/hour), was injected intravenously into male Sprague-Dawley rats. RNA was extracted from oxyntic mucosa, and heparin-binding epidermal growth factor-like growth factor and related peptide gene expression was estimated using a ribonuclease protection assay. The level of transforming growth factor-alpha mRNA did not change at any time point during the experiment. In contrast, the levels of heparin-binding epidermal growth factor-like growth factor and amphiregulin mRNA were significantly increased within 3 hours following gastrin infusion and reached maximum levels 6 and 12 hours later, respectively. Continuous infusion of gastrin significantly increased oxyntic mucosal proliferation. Gastrin receptor antagonist significantly inhibited gastrin-induced heparin-binding epidermal growth factor-like growth factor and amphiregulin gene expression and gastrin-induced oxyntic mucosal proliferation. These findings indicate that heparin-binding epidermal growth factor-like growth factor and amphiregulin genes are induced by gastrin and that they play a role in the trophic action of gastrin on oxyntic mucosa.

Amphiregulin

Analysis of the Rb gene and cyclin-dependent kinase 4 inhibitor genes (p16INK4 and p15INK4B) in human ovarian carcinoma cell lines.

In the present study, we analyzed human ovarian carcinoma cell lines for abnormalities in the tumor suppressor gene Rb (retinoblastoma) and in cyclin-dependent kinase 4 (CDK4) inhibitor genes (p16INK4 and p15INK4B) using molecular biology techniques. For the Rb gene, in all six cell lines (PA-1, Caov-3 and -4, OVCAR-3, SK-OV-3, and Kuramochi), Rb gene abnormality was not detected using Southern blotting. In the Caov-3 cell line transcripts were not detectable by either Northern blot or polymerase chain reaction. Sequence analysis of the entire coding region of the Rb gene revealed point mutations (AAC to GAC) resulting in codon 123 (Asn to Asp) changes in the Caov-4 cell line. In the PA-1 cell line both wild-type Rb and mutant-type Rb (codon 798: CGG to TGG) were expressed, and in the OVCAR-3 cell line both wild-type Rb and mutant-type Rb (codon 704: ATG to GTG) were expressed. In four of six human ovarian carcinoma cell lines Rb gene abnormality was detected. For the p16INK4 and p15INK4B genes, only the SK-OV-3 cell line had abnormalities. There was a gene rearrangement or minor deletion of the p16INK4 gene in the SK-OV-3 cell line, while the p15INK4B gene was deleted in this cell line. In the SK-OV-3 cell line no mRNAs of p16INK4 and p15INK4B were expressed. At the point of Rb gene inactivation, we can explain five cell lines of six: four cell lines had abnormalities in the Rb gene itself, which is another mechanism by which the Rb gene is inactivated, while one cell line (SK-OV-3) had abnormalities in CDK4 inhibitor genes, another of the inactivation mechanisms of the Rb gene. These data suggest that abnormalities of Rb and CDK4 inhibitor genes (p16INK4, p15INK4B) may be involved in human ovarian carcinogenesis.

Carcinoma

Proteolytic activation of a putative receptor leading to vasoconstriction and platelet aggregation.

Submandibular enzymatic vasoconstrictor (SEV), a member of the kallikrein family of enzymes, elicits biological effects by a proteolytically mediated mechanism. We studied 1) whether SEV is able to aggregate platelets and 2) whether SEV may activate a receptor other than the cloned thrombin receptor. SEV (10(-8)M) aggregated platelets, released ATP and increased intracellular Ca2+. Elastase treatment rendered human platelets unresponsive to SEV and thrombin (TH), but not to cathepsin G. In desensitization experiments performed with gamma-TH, after two successive additions of approximately 50 nM gamma-TH, a third dose elicited 15.8 +/- 3.4% of the initial response (n = 4), but platelets responded to approximately 20 nM SEV by 33.8 +/- 7.2% of control (p < 0.03 vs last response to gamma-TH). After desensitization to SEV (n = 4), the response to a third dose was 4 +/- 1.3% of control, but gamma-TH still induced 37.7 +/- 12.4% aggregation (p < 0.02 vs last response to SEV). Incubation of washed rabbit platelets with alpha-TH digested with elastase (10(-10) M TH added to 7 micrograms/ml elastase for 1 min) rendered them unresponsive to additional challenges with TH, but they still responded to an equipotent dose of SEV (2.7 x 10(-9) M) by 86 +/- 48% of control. In isolated rabbit aortic rings contracted with 10(-6) M norepinephrine (NE) to 42 +/- 3% of maximum. SEV (2.8 x 10(-8) M) caused further contraction to 87 +/- 4%. In contrast, alpha-TH (1.6 x 10(-7) M) tended to relax both NE- and SEV-contracted rings by 14 +/- 2 and 16.2 +/- 2%, respectively (n = 3 each). We concluded that part of the platelet-aggregating effect of SEV may be mediated by activation of a receptor(s) different from that of TH.

Animals

Activation of salmon GnRH mRNA expression prior to differentiation of precocious males in Masu salmon.

Changes in salmon gonadotropin-releasing hormone (sGnRH) mRNA levels in the brain of underyearling male masu salmon, Oncorhynchus masou, were investigated to clarify sGnRH participation in differentiation of precocious males. Fish were immature with low gonadosomatic index (GSI < 0.100%) on April 16 and May 7. On June 11, fish were differentiated into two groups: future precocious males and immature males. Fish in the former group had high GSI (0.203%) with proliferation of primary spermatocytes in the testis, while the latter had low GSI (0.055%) with primary spermatogonia. sGnRH mRNA levels (the number of neurons expressing sGnRH mRNA and the total number of silver grains per unit area) in the ventral telencephalon (VT) and in the VT plus preoptic area (POA) already increased in May before the differentiation of precocious males. GSI was positively correlated with sGnRH mRNA levels in the VT and in the VT plus POA in April, and with mRNA levels in the POA in May. Activated sGnRH synthesis is concluded to be related to the appearance of precocious males in masu salmon.

Animals

Transtrochanteric rotational osteotomy for osteonecrosis of the femoral head. 43 patients followed for at least 3 years.

We reviewed 48 hips in 43 patients 3-7.1 years (average 4.6 years) after Sugioka transtrochanteric rotational osteotomy for osteonecrosis of the femoral head. The average age at operation was 41 years. Thirty-four patients were men and 9 women. Overall results at the final follow-up were satisfactory in 30 hips (62%). Kaplan-Meier's survivorship was 62% at 3 years and 60% at 5 years postoperatively. Six hips for which the ratio of the intact area of the articular surface on the preoperative lateral radiograph was less than 30% showed further collapse. Five hips were converted to bipolar hemiarthroplasties or total hip arthroplasties. Complications, such as varus deformity, subtrochanteric fracture, and ectopic bone formation, occurred in eight hips. Five of them were operated on in the first 2 years of this series. Three of these five operations had unsatisfactory results. We conclude that satisfactory results can be achieved using this osteotomy by maintaining exact surgical technique and by limiting the surgical indications to hips with an intact area of more than one-third of the entire articular surface on the lateral radiograph of the femoral head.

Adolescent

Successful treatment of intraoperative pulmonary tumor embolism from renal cell carcinoma.

During left nephrectomy in a 35-year-old woman with a left renal cell carcinoma extending into the inferior vena cava (IVC) and right atrium, cardiac arrest occurred. Immediate transesophageal echocardiography demonstrated that the event was caused by a pulmonary tumor embolism. Emergent cardiopulmonary bypass (CPB) was established and the tumors in the pulmonary arteries were successfully removed. The left nephrectomy was completed. The patient recovered in the intensive care unit without any neurological deficit. A postoperative pulmonary perfusion scintigram showed no defect in the pulmonary circulation. Transesophageal echocardiography was useful for making a rapid diagnosis of an intraoperative pulmonary embolism originating from a tumor of the IVC or right atrium.

Adult

Acute lupus peritonitis successfully treated with steroid pulse therapy.

A 21-year-old man with systemic lupus erythematosus (SLE) who developed acute lupus peritonitis is described. Acute lupus peritonitis appeared during generalized lupus flare, with nausea, vomiting, frequent diarrhea, and abdominal tenderness with rebound and guarding. The patient was afebrile and had decreased bowel sounds. Abdominal ultrasonography and computed tomography revealed marked thickening of the gastric, duodenal, and jejunal walls, massive intraluminal fluid collection, and increasing ascites. Gastrointestinal endoscopy showed edematous mucosa with multiple erosions of the stomach and duodenum. The ascitic fluid was remarkable for low complement levels and elevated anti-DNA antibody. These manifestations of acute lupus peritonitis resolved after steroid pulse therapy with methylprednisolone. We should consider acute lupus peritonitis in a patient with SLE when abdominal symptoms are severe. Experience with our patient indicates that steroid pulse therapy is effective for this rare but severe manifestation of SLE.

Acute Disease

Comparative rest and exercise hemodynamics of allograft and prosthetic valves in the aortic position.

BACKGROUND: Allograft aortic valve replacement has gained widespread acceptance. However, there is little information about in vivo allograft valve function at rest and during exercise. METHODS: Cardiac catheterization was performed to measure hemodynamic variables at rest and during supine bicycle exercise in 44 patients who had had aortic valve replacement using allograft valves or Bicer or St. Jude Medical prosthetic valves 19 to 27 mm in diameter. Sixteen patients received an allograft valve; 17, a Bicer valve; and 11, a St. Jude Medical valve. There were no significant differences between the three groups in age, body surface area, left ventricular end-systolic and end-diastolic volume indices, exercise cardiac index, exercise heart rate, or work load achieved. Left ventricular and ascending aortic pressures were measured simultaneously according to the transseptal method. RESULTS: The mean pressure gradient was generally higher for the Bicer and St. Jude Medical valves than for the allograft valves, both at rest and during exercise. Significant differences were obtained in patients with small-sized valves (21 and 23 mm); pressure gradients were higher in the prosthetic valve groups. In patients with large-sized prosthetic valves (25 mm), there were no significant differences between the three groups at rest and during exercise. However, there was no pressure gradient at all for allograft valves. CONCLUSIONS: Exercise cardiac catheterization confirms that the allograft aortic valve is an ideal substitute from the hemodynamic aspect, particularly in patients with a small aortic root and in those who perform strenuous exercise.

Aortic Valve

Transplantation of genetically marked cardiac muscle cells.

We examined the possibility that cardiomyocytes could be genetically marked or modified before being grafted to the heart under conditions applicable to the clinical setting. We used a replication-defective recombinant adenovirus carrying the beta-galactosidase reporter gene, and delivered it to cultured murine fetal cardiac myocytes. Virtually all fetal cardiomyocytes in a primary culture expressed beta-galactosidase 24 hours after recombinant adenovirus infection. These cells were transplanted to the hearts of syngenic adult recipient mice. Expression of the beta-galactosidase gene in the grafted cells was demonstrated by staining with 5-bromo-4-chloro-3-indoyl-beta-D-galactosidase, resulting in a blue color at the histochemical level and an electron-dense deposit on transmission electron microscopic analysis. Gene expression was recognized from 7 days to 12 weeks after transplantation. Implanted cardiomyocytes aligned themselves along the layers of the host myocardium. Formation of gap junctions was demonstrated by transmission electron microscopy. Neither inflammation nor fibrous scar tissue was detectable by histologic analysis. This study demonstrates that ex vivo gene transfer to the heart by means of the adenoviral vector is possible.

Adenoviridae