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Biomedical subjects

T Kuwabara

Publications and source records attributed to T Kuwabara.

At least 271 records · Page 15Linked to original sources
PubMed1982

Studies on the designing of chemotherapy for gastric cancer in man, based on the tumor tissue concentration of anticancer agents.

5-fluorouracil analogs investigated in this study include a combination of uracil and Ftorafur (UFT), Ethyl (+/-)-t-butoxy-5-fluoro-hexahydro-2, 4-dioxopyrimidine r-5-carboxylate (TAC-278), and 5'-deoxy-5-fluorouridine (5'-DFUR). In a total of 45 patients with gastric cancer, tumor tissue level of 5-fluorouracil (5-FU) was determined at 2, 4, 6, 8, and 12 hours following the oral administration of drug, using a resected stomach specimen as material. As a result, it was demonstrated that oral administration of 200 mg/m2 of UFT maintained above 0.05 microgram/g (minimum inhibitory concentration: MIC) of 5-FU in tumor tissues over 12 hours in 11 of 13 patients. On the contrary, 133 mg/m2 of TAC-278, and 200 mg/m2 or 300 mg/m2 of 5'-DFUR (which is activated by thymidine phosphorylase in man) did not produce an effective 5-FU concentration in tumor tissues. Serum 5-FU level was high in order of TAC-278, UFT, and 5'-DFUR. Clinical response rates obtained with UFT (200 mg/m2 twice a day), or TAC-278 (133-200 mg/m2, 3 times daily) were 27.5% (49 of 178 cases), and 8.3% (3 of 36 cases, by Koyama et al.), respectively. Fisher's direct probability test revealed that there was a significant difference (p less than 0.05) between them in the response rate. It was considered that the measurement of concentration of anticancer drugs in tumor tissues might provide us useful information for the designing of chemotherapy of gastric cancer.

Antineoplastic Agents↗
PubMed1982

The roles of vitamin E and unsaturated fatty acids in the visual process.

Relatively high proportions of long-chain, polyunsaturated fatty acids seem to be required in rod photoreceptor membranes in order to provide the precise microenvironment for the proper function of the visual pigment rhodopsin. At the same time, such high levels of lipid unsaturation put the photoreceptor membranes at a high risk for autoxidation. The antioxidant vitamin E which can minimize autoxidation of polyunsaturated fatty acids is found in rather high concentrations in the outer segment membranes. Dietary deficiency in vitamin E induces disintegration of rod outer segment membranes, probably by increasing autoxidation. Also, it greatly accelerates the accumulation of aging pigments in the retinal pigment epithelium, probably because these lipofuscin granules do indeed represent the end products of lipid peroxidation. Vitamin E supplements, up to threefold normal levels, appear to provide no significant protection of the retina from light damage produced either by short but acute or by long-term, low level exposures to light. This is not consistent with current theories which implicate lipid peroxidation in the destruction of rod outer segments in light damaged retinas; more work is needed before any relation between retinal light damage and vitamin E levels can be assessed. Surprisingly, the amount of lipofuscin granule accumulation in the retinal pigment epithelium is influenced dramatically by dietary levels of vitamin A. Even retinas lacking a source of polyunsaturated fatty acids from rod outer segments still may accumulate massive lipofuscin if dietary vitamin A is provided. Perhaps vitamin A, which has such a dynamic relationship with the retinal pigment epithelium, becomes oxidized, and then contributes to the formation of a lipofuscin-like pigment. Centrophenoxine, a drug claimed to be effective in reversing the accumulation of age-related lipofuscin in the central nervous system, has no obvious effect in the eye or uterus in removing the lipofuscin granules induced by vitamin E deficiency. Microperoxisomes are abundant in the retinal pigment epithelium, and may be associated with rapid lipid turnover and/or utilization of lipid soluble vitamins. Their potential roles, however, need further documentation and clarification. Recently developed techniques and new discoveries in lipid research open the way for many fruitful studies on the interactions and precise roles of lipids and lipid-soluble vitamins in vision.

Animals↗
PubMed1982

Galactose cataract prevention with sorbinil, an aldose reductase inhibitor: a light microscopic study.

Cataract formation in galactosemic rats was studied by ophthalmoscopy, slit-lamp biomicroscopy, and by light microscopy using plastic embedding with methacrylate. Untreated rats developed nuclear cataracts by 14 days and mature cataracts by 21 days. However, rats treated with the aldose reductase inhibitor sorbinil did not develop any cataractous change for up to 8 months of 50% galactose feeding and could not be distinguished from normal controls. This strongly suggests that aldose reductase is the common factor involved in the formation of sugar cataracts.

Aldehyde Reductase↗
PubMed1982

Intrinsic, light-independent, regional differences in photoreceptor cell degeneration in vitamin A-deficient rat retinas.

The retinas of retinol-deficient rats reared in darkness or cyclic light were examined to determine whether regional degeneration of photoreceptor cells was induced by environmental lighting or resulted from intrinsic differences between ocular hemispheres. Weanling male Sprague-Dawley rats were fed a retinol-adequate or retinol-deficient diet and were reared in either cyclic light or darkness through 29 weeks. The nasal retinal quadrants were examined by light microscopy and the number of photoreceptor nuclei was counted in a 630 micron segment beginning 200 micron from the optic nerve. Retinol-deficient rats reared in darkness for 29 weeks lost 24% of their photoreceptors in the inferior nasal quadrant but only 11% in the superior nasal quadrant. Deficient rats reared in cyclic light for 29 weeks lost 39% of their photoreceptor cells in the inferior nasal quadrant and only 16% in the superior nasal quadrant. Photoreceptor cells degenerated faster in the inferior nasal quadrant than in the superior nasal quadrant in darkness or cyclic light. These results indicate that regional differences in rate of photoreceptor cell loss in retinol-deficient rats are not induced by the lighting conditions but occur as a result of intrinsic differences between the ocular hemispheres.

Animals↗
PubMed1982

[Astroblastoma in newborn baby (author's transl)].

A case of astroblastoma in a male newborn baby was reported. He has been suffered from convulsive seizures from six hours later after the birth, not controlled by the anticonvulsants, and lumbar tap revealed bloody cerebrospinal fluid. He had no response against the noxious stimuli and left clonic hemiconvulsion, and showed anisocoria, left pupil was dilated. Right BAG showed a large space occupying lesion in the right frontal lobe. Operation was performed eighteen hours after the birth. Right frontotemporal craniotomy revealed reddish-grey, soft tumor in the right frontal lobe infiltrating into the parietal and temporal lobe of the same side and frontal lobe of the left side. Right frontal lobectomy was performed. He had cardiac arrhythmia after the operation and died next day. Autopsy was not permitted. Histologically tumor tissue showed abundant vessels and perivascular pseudorosettes, and electron micrograph revealed glial filaments in the tumor cells. Histological diagnosis was astroblastoma.

Astrocytoma↗
PubMed1981

S-antigen uveitis in primates. A new model for human disease.

Uveitis was induced rhesus monkeys immunized with purified retinal S-antigen. Focal retinal and subretinal infiltration, in addition to periphlebitic changes, were observed histologically. Immunized monkeys had similar cell-mediated in vitro immune responses to the S-antigen as do humans with posterior uveitis. Circulating immune complexes at the time of disease could not be detected. This primate model supports the notion that the S-antigen may play a role in human uveitis.

Animals↗
PubMed1981

Experimental model of gyrate atrophy in animals.

Intravitreal injection of L-ornithine hydrochloride in physiologic saline solution caused marked edema specifically in the pigment epithelium of Sprague-Dawley strain albino and Evans black hooded rats and rhesus and cynomologus monkeys. Swelling of the pigment epithelial cells, which was most prominent four hours after the injection, disappeared by 24 hours. However, many pigment epithelial cells gradually degenerated resulting in patches of denuded areas. The photoreceptor cells overlying the damaged pigment epithelium degenerated secondarily.

Animals↗
PubMed1981

Systemic manifestations of gyrate atrophy of the choroid and retina.

In ten patients with gyrate atrophy (GA) and hyperornithinemia, the head hair was fine, straight, and sparse. On microscopic examination, both scalp and pubic hair contained intermittent dark cores within the medullary zone, which was not a deposit, but appeared to be due to the unusual refractive properties of loosely formed macrofilaments amidst wide spaces containing a structureless electron lucent but compact substance, which was insoluble in both water and solvents. Seven of the ten patients had abnormal wave forms on electroencephalography. Three of the five patients who underwent muscle biopsy had tubular aggregates. Of particular interest was the toxicity of exogenous ornithine added to muscle cell culture from GA patients as compared with the lack of toxicity in muscle from control patients. What specific role the hyperornithinemia and absence of OAT is playing in the histopathology of hair and muscle and the EEG changes awaits further biochemical investigation.

Adolescent↗
PubMed1981

In utero allogeneic bone transplantation in primates: roentgenographic and histological observations.

Intrauterine allogeneic bone transplantation was performed on 25 monkey fetuses at 120 to 135 days of gestation. Two surgical techniques for orthotopic transplantation of the humeral midshaft were utilized: (1) A segment (5 to 7 mm) of fetal humerus was transplanted from fetus (donor) to fetus (recipient). An intramedullary pin (Kirschner orthopedic wire) was used for fixation of the severed humerus. (2) Without severing the humerus, a midshaft area (5 to 7 mm X 5 to 6 mm) was surgically ablated. A bone paste composed of crushed bone particles mixed with an agar-enriched culture medium was sculpted to fill this lesion. We used fresh frozen or fresh allograft tissue with equal success. Postsurgical observations included serial roentgenographic and histological evaluation of humeral osteogenesis, as well as postnatal assessment of limb use. The contralateral arm served as a control. Our findings indicate that the immune surveillance system of fetal monkeys may be tolerant of these bone allografts; alternatively, healing by substitution may also occur. The roentgenographic and histological results demonstrate that both of the transplantation procedures used here achieved restoration of the long bone. The use of bone paste allowed us to sculpt the allograft to the desired conformation. These results from laboratory primate models encourage continued investigation of fetal allogeneic bone transplantation, because of its ultimate potential for intrauterine repair of skeletal anomalies in man.

Animals↗
PubMed1981

Pathogenicity of Spiroplasma sp. strain SMCA in Syrian hamsters: clinical, microbiological, and histological aspects.

The intracerebral inoculation of newborn Syrian hamsters with pure cultures of Spiroplasma sp. strain SMCA caused severe, prolonged disease involving the central nervous system, culminating in death. The disease was characterized by spasms, muscular tremors, disturbances in motor control, inability to feed, dramatic loss of weight, and runting. The effect ws dose related, with the largest numbers of viable spiroplasmas producing the highest incidence of disease and death in the shortest period of time. Severe hemorrhaging developed throughout the brain, liver, and spleen, and spiroplasmas were readily recovered from these organs, indicating that the agent disseminated from the initial site of infection to distant host tissues. Newborn animals were susceptible, but adults were resistant; these findings are similar to those reported for newborn mice and rats. Unlike mice and rats, hamsters did not develop cataracts visible to the unaided eye. The histopathological features of eye disease in hamsters were different from those in rats and were characterized by microophthalmia (especially in runted hamsters) and abnormal proliferation, disorientation, and disorganization of corneal, lens, and retinal tissues. The significance of these findings is discussed.

Animals↗
PubMed1981

Resemblance between rhodopsin kinase and S-antigen induced uveitis.

The retinal S-antigen (S-Ag) has been shown to induce uveitis effectively in subhuman primates, and lymphocytes from patients with certain uveitic conditions show cell-mediated responses to this antigen. Rhodopsin kinase (RK), an enzyme probably unique to the mammalian eye, is reported here to resemble the retinal S-Ag in its capacity to induce uveitis in experimental animals. A histological comparison of rat eyes taken 2 and 3 weeks after immunisation with either RK or S-Ag reveals essentially identical pathological alterations. Ocular inflammation is seen in both the anterior and posterior portion of the globe. Areas of focal degeneration of the photo-receptor layer, from which both the S-Ag and RK are extracted, could be seen in both RK and S-Ag immunised animals. Cells from draining lymph nodes of both groups responded by increased thymidine incorporation when cultured in the presence of either RK or S-Ag. In addition antibodies directed against the S-Ag were detected in both groups. These findings, in addition to the biochemical similarities of these preparations, reported elsewhere, would strongly suggest that RK and S-Ag are one and the same. The identification of potentially uveitogenic ocular antigens could help to reclassify uveitic entities that at present have clinically similar courses.

Animals↗