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Biomedical subjects

M Kitahara

Publications and source records attributed to M Kitahara.

At least 127 records · Page 7Linked to original sources

[An experience of single dose captopril renal scintigraphy in the diagnosis and management of bilateral renovascular hypertension].

A 41-year-old woman visited our hospital with chief complaint of hypertension which was refractory to multiple antihypertensive drugs. Her blood pressure was 200/140 mmHg and her plasma renin activity was as high as 3.1 ng/ml/hr. Angiography revealed bilateral renal artery stenosis. To determine the laterality of the kidney which were responsible for her hypertension, the 99mTc-DTPA renal scintigraphy with captopril was performed. The estimated GFR of the right kidney was lowered than that of the control, while there was no change in the left kidney. Subsequently Percutaneous Transluminal Angioplasty (PTA) was performed to the right kidney. Postoperatively blood pressure remained elevated as well as serum renin level. 99mTc-DTPA scintigraphy with captopril was repeated and revealed no decrease in the GFR of the right kidney this time, but significant reduction in the GFR of the left kidney. After the second PTA to the left kidney, her blood pressure was finally normalized. Postoperatively GFR of both kidneys was not affected by captopril on renal scintigraphy, and currently she has remained normotensive without medication. 99mTc-DTPA scintigraphy with captopril appears to be a useful method to diagnose the laterality and to evaluate in clinical response to therapeutic intervention.

Adult↗

Preparation of new 7-hydroxyguanine derivatives and their biological activities.

We prepared new 7-hydroxyguanine derivatives, 7-hydroxyguanosine 5'-monophosphate and N2-tetrahydropyranyl-7-hydroxyguanine, and compared biological activities of 7-hydroxyguanine derivatives including nucleosides acquired previously. 7-Hydroxyguanine and its nucleotide inhibited the focus formation of Rous sarcoma virus. Antitumor activities of these derivatives against mouse leukemia L1210 were not so different from one another. Anti-proliferative activities of the derivatives on various human cell lines were significantly different from one another.

Animals↗

Extracellular recording of vestibulo-thalamic neurons projecting to the spinal cord in the cat.

Forty vestibulo-thalamic (VT) neurons were recorded extracellularly in the vestibular nuclei of the anesthetized cat. More than half of the VT neurons responded monosynaptically to vestibular nerve stimulation; the others responded polysynaptically. The VT neurons were activated antidromically from one or two sites in the contralateral VPL, VPM, VL, VM, SG, and PO in the thalamus. Their axonal arborizations in the thalamus were likely restricted in narrow areas. About three quarters of the VT neurons were also activated antidromically from the ventral funiculus in the C1 segment. Axonal branchings were found in the contralateral C1 gray matter. The VT neurons were mainly localized in the descending vestibular nucleus.

Animals↗

Augmentative effect of Nocardia rubra cell-wall skeleton on the induction of human lymphokine-activated killer (LAK) cells by the production of LAK cell helper factor(s).

Nocardia rubra cell wall skeleton (N-CWS) was found to synergistically augment lymphokine-activated killer (LAK) cell generation from human peripheral blood mononuclear cells (PBMC) in the presence of a suboptimal dose of recombinant interleukin-2 (rIL-2). N-CWS increased the number of PBMC expressing IL-2 receptor on their surfaces, and the presence of N-CWS at the early stage of the culture period was essential for the exertion of its augmentative activity on the LAK induction. The predominant phenotype of LAK precursor cells responding to N-CWS and rIL-2 was CD3- CD16+. Culture supernatant from N-CWS-stimulated PBMC was found to act as a substitute for N-CWS in the induction of LAK generation in the presence of rIL-2, suggesting that these cells produced a factor capable of augmenting LAK cell induction (LAK helper factor, LHF). LHF was found to have a molecular mass of 29 kDa by gel filtration, and could also function as a killer helper factor to augment allo-antigen-specific cytotoxic T lymphocyte generation from human peripheral blood T cells as well as murine thymocytes. LHF showed no species specificity, indicating that it is different from IL-4. The enhancing activity of LHF was not neutralized with anti-TNF alpha, anti-IL-1 alpha, or anti-IL-1 beta antibodies. Furthermore, no tumor necrosis factor-alpha (TNF alpha), TNF beta, IL-1 alpha, beta, IL-2, IL-5, IL-6 or interferon activity was detected in semi-purified LHF during enzyme-linked immunosorbant assay and biological assays. The present findings indicate that LHF produced from N-CWS-stimulated PBMC is a molecule distinct from TNF alpha, TNF beta, interferon, IL-1, -2, -4, -5, and -6, and suggest that LHF might be a novel lymphokine involved in LAK generation.

Adjuvants, Immunologic↗

Enhancement of therapeutic effect of interleukin-2 on spontaneous pulmonary metastases of Lewis lung carcinoma by killer helper factor associated with increased induction of killer activity.

Killer helper factor (KHF) was previously found to be produced by a human T cell hybridoma, 24A . CA2. We studied the therapeutic effects of interleukin-2 (IL-2) and KHF on the inhibition of pulmonary metastases of syngeneic Lewis lung carcinoma (3LL) in C57BL/6N mice. Multiple subcutaneous (sc) injections of IL-2 plus KHF had significantly more effect than injections of IL-2 alone in inhibiting spontaneous pulmonary metastases and prolonging survival of the mice. The effect of KHF with IL-2 on induction of lymphokine (IL-2)-activated killer (LAK) activity against P-29 cells was examined in the murine system. Spleen cells generated LAK activity after incubation for 4 days with more than 500 U/ml of IL-2. In contrast, KHF alone did not render spleen cells cytotoxic. The combination of these lymphokines at subthreshold concentrations, however, resulted in significant in vitro induction of LAK activity. The LAK activity of splenocytes incubated with IL-2 plus KHF was maximal after 4 days, and persisted for longer than that of cells treated with IL-2 alone. The LAK cells induced by KHF plus IL-2 were also cytotoxic to FBL and YAC-1 cells. Moreover, spleen cells of mice bearing lung metastases could be induced to the cytotoxic state by sc injections of IL-2 plus KHF. These results indicate that combination treatment with IL-2 and the new lymphokine KHF should be useful clinically in inducing LAK activity for inhibition of pulmonary metastases.

Animals↗

[Enhancement of the effect of X-irradiation against cultured human glioblastoma cells by pretreatment with ACNU].

Human glioblastoma A-7 (GB A-7) cells can apparently recover from potentially lethal X-irradiation. The authors, using a colony-forming assay, studied the influence of pretreatment with 1-(4-amino-2-methyl-5-pyrimidinyl) methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride (ACNU) on the effectiveness of X-irradiation against GB A-7 cells grown in monolayers and as multicellular spheroids. Pre-exposure to ACNU inhibited the recovery of irradiated GB A-7 cells. In monolayer cells, the combination treatment was most effective when ACNU was applied 2 to 8 hours prior to irradiation, and the larger the X-ray dose, the more potent the effect. ACNU pretreatment was more effective against large spheroids (enhancement ratio 1.86) than against small ones (1.34). Large spheroids showed necrosis, whereas small ones did not. Isobolographic analysis disclosed that the effect of combining X-irradiation and ACNU is within an additive envelope at the surviving fraction of 10(-2), while supra-additive at the surviving fraction of 10(-3). These results suggest that the potency of X-irradiation is augmented by ACNU pretreatment through an interactive mechanism. Further, suppression of recovery from X-ray induced potentially lethal damage was influenced by the presence of necrosis.

Brain Neoplasms↗

Immunofluorescent study of the endolymphatic sac in Menière's disease.

Immunofluorescent and light microscopic studies were performed on 21 small endolymphatic sac specimens biopsied during endolymphatic sac drainage surgery. The biopsies were taken from the extraosseous portions of the lateral side of the sac. Of the 21 specimens, only 5 displayed prominent histologic signs, including 1 with brown pigmentation and 4 with positive immunofluorescent reactions to either IgG, IgA, or IgM. No such histologic signs were seen in any of the other 16 specimens, although severe fibrous tissue change was found. One of the 4 specimens showing immunofluorescent reactions displayed a triple-layered ring structure in which the outer layer was IgM positive, the middle layer IgG positive, and the inner layer IgA positive (case 1). This ring-like structure, located in the fibrous tissue, appeared to be an occluded blood vessel. Another specimen showed positive reactions to IgG and IgA in a section which appeared to be part of the lumen, and which contained a macrophage-like cell and a lymphocyte. These results tend to support the idea that certain types of Meniere's disease are caused by immunologic injuries to the endolymphatic sac.

Adult↗

Compensation of otolith function.

Horizontal eye displacement in total darkness during lateral tilting about the body axis was examined in 14 patients with unilateral loss of labyrinth function, including 8 cases of positional vertigo or dizziness and 6 symptom-free cases. The change in eye displacement following labyrinthectomy was also studied in 2 cases of labyrinthitis and one case of delayed hydrops. Seven out of 8 subjects suffering from positional vertigo or dizziness exhibited abnormal eye displacement on tilting to the affected side, while 5 out of 6 symptom-free subjects showed normal eye displacement. The correlation between anomalous eye displacement and the presence of subjective symptoms was statistically significant (p less than 0.05). Abnormal eye displacement following labyrinthectomy was readily noted within 2 weeks of surgery, but became almost undetectable 3 to 4 weeks postoperatively, in close accordance with a decrease in positional vertigo or dizziness. It was concluded that the measurement of eye displacement during lateral body tilt, although previously reported to be useful in the assessment of function, might also be employed to examine compensation for the loss of otolith function.

Adaptation, Physiological↗

IL-6/BSF-2 functions as a killer helper factor in the in vitro induction of cytotoxic T cells.

rIL-6/B cell stimulatory factor 2 was found to augment CTL generation from mature as well as immature human T cells stimulated with UV-treated allogeneic cells. rIL-6 also acted on peanut agglutinin-positive murine thymocytes and Lyt-2-positive splenic T cells to give rise to CTL. rIL-6 alone could not induce CTL generation, the presence of IL-2 during the early phase of culture period was found to be essential for the IL-6 activity in the induction of CTL. The effect of rIL-6 was not mediated by the induction of IL-2 inasmuch as rIL-6 did not augment IL-2 production in MLC and anti-IL-2 antibody could not neutralize IL-6 activity. rIL-6 augmented CTL generation even when added 72 h after the initiation of cultures. The enhancing activity of rIL-6 could be neutralized with anti-IL-6 antibodies even when added 72 h after the initiation of cultures. The present data indicate that IL-6 acts in the late phase of CTL generation.

Adjuvants, Immunologic↗

Determination of oxidizable inorganic anions by high-performance liquid chromatography with fluorescence detection and application to the determination of salivary nitrite and thiocyanate and serum thiocyanate.

A sensitive method for the simultaneous determination of oxidizable inorganic anions (sulphide, thiocyanate, thiosulphate and nitrite) was developed by use of high-performance liquid chromatography and fluorimetric detection based on the formation of fluorescent cerium(III) by a redox reaction with cerium(IV). The detection limits are 0.1 nmol for both thiocyanate and nitrite, 0.3 nmol for thiosulphate and 0.8 nmol for sulphide per 10-microliters injection volume. This system can be utilized for the determination of salivary thiocyanate and nitrite and serum thiocyanate.

Anions↗

Experiences with CT-guided stereotaxic biopsies in 121 cases.

Needle biopsy using a CT-guided stereotaxic technique was performed in 121 cases of suspected brain tumour. Using this technique, it is possible to perform biopsies safely and accurately on even small and deep-seated lesions with a minimum of surgical intervention. However, accurate diagnoses are sometimes not possible when only a small number of viable cells are obtained, such as in lesions containing old haematoma, cystic tumours, previously treated tumours or tumours which are either too hard or too soft. We were able to make accurate diagnoses in 98 of our 121 cases (81%). The accuracy of diagnosis is somewhat hampered by the small volume of sample material obtained using this biopsy technique, and this fact should be kept in mind when evaluating the histological material.

Adolescent↗

[Biological basis for combined radio-chemotherapy in radioresistant tumors].

Human tumor cells such as melanoma or glioblastoma are intrinsically radioresistant on an average than cells of more common tumors in radiotherapy such as squamous cell carcinoma or adenocarcinoma. Mean inactivation dose (D) for glioblastoma A-7 cells was 3.1 Gy for cells growing exponentially, but was 4.3 Gy for cells grown in large spheroids with hypoxic cells and PLD recovery. The D for cells of squamous cell carcinoma was about 2.1 Gy. This indicates that local control of the radioresistant tumors may be achieved if a drug showing an enhancement ratio of about 2.0. Data on our experiments with others in the literature indicate that drugs which selectively sensitize hypoxic cells and inhibit PLD recovery may be useful to increase the therapeutic ratio. Experimental evidence on a nitrosourea, ACNU has been presented for such mechanisms of the action. Multivariate analysis with Cox's model on malignant gliomas of 209 patients indicated that a significant increase in the survival time was obtained in the radiotherapy combined with ACNU.

Antineoplastic Agents↗

[Persistent primitive first cervical intersegmental artery (proatlantal artery II) with occlusion of the basilar artery--a case report].

A rare case of persistent primitive first cervical intersegmental artery (proatlantal artery II) is reported. A 58-year-old man was admitted to our hospital with dysarthria and left hemiparesis. On admission he was stuporous with bilateral gaze palsy and left hemiparesis. CT scan on admission showed low density areas in the right cerebellar hemisphere and ventricular part of the pons. Right retrograde brachiography revealed occlusion of the basilar artery, aplasia of the right vertebral artery and an abnormal vessel connecting the right external carotid artery and the right vertebral artery. This anastomotic vessel was thought to be a persistent primitive first cervical intersegmental artery (Proatlantal artery II). Left carotid angiography revealed the left posterior cerebral artery was visualized through the posterior communicating artery, leading from the internal carotid artery. Left retrograde brachial angiography showed that the left vertebral artery terminated just distal from the branching of the left posterior inferior cerebellar artery. After admission the left hemiparesis deteriorated gradually and tracheotomy was done due to respiratory difficulties. The patient was then transferred to the rehabilitation center on his 34th day in hospital with neurological deficits.

Arterial Occlusive Diseases↗