Biomedical subjects
Publications and source records attributed to T Hara.
Sixteen patients who underwent transurethral resection of prostate preoperatively received intravenous injection of cefmetazole in a doses of 2 gram. Pharmacokinetic study revealed that concentration of cefmetazole in prostatic tissue well correlated to serum concentration with nearly the same half-life times.
Patients received 2 gram of cefmetazole, twice on the day of transurethral prostatectomy and the next day, once for the succeeding 2 days. Thirteen out of 34 cases showed significant preoperative bacteriuria. Only 3 of them persisted on the 5th day. Postoperative courses were uneventful in all cases with neither acute epididymitis nor significant fever.
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A covalent conjugate of avidin with ricin subunit A-chain (avidin-RA) was prepared by using N-succinimidyl 3-(2-pyridyldithio)propionate as a coupling agent. Selective cytotoxic activity after the combined treatment of spleen cells with biotinylated antibody and avidin-RA was demonstrated by the fact that the responsiveness to LPS was selectively abrogated by pretreatment of the cells with biotinylated rabbit anti-mouse immunoglobulin (MIg) antibody, but not with biotinylated anti-Thy-1.2 antibody. Neither the biotinylated antibody alone nor avidin-RA alone was effective in decreasing the responses to mitogens. Moreover, a high anti-DNP PFC response elicited by DNP-KLH-primed BALB/c mouse spleen cells stimulated in vitro with DNP-KLH was mostly abrogated by the pretreatment of the cells with biotinylated anti-MIg antibody and avidin-RA. Again, neither the biotinylated antibody alone nor avidin-RA alone was effective in decreasing the anti-DNP PFC response. This cell-killing method with the use of biotinylated antibody and avidin-RA was applied and evaluated in experimental systems in which the helper action of T cells on B cells was mediated by T cell-replacing factor (TRF) or was performed by the direct interaction of T cells with B cells (cognate interaction). When DNP-KLH-primed splenic B cells, pretreated with biotinylated F(ab')2 fragment of DCF1 male anti-BALB/c-B IgG antibody against acceptor site(s) for TRF followed by treatment with avidin-RA, were stimulated with DNP-OVA in the presence of monoclonal TRF, the anti-DNP PFC response was significantly decreased, whereas the same treated B cells responded well to stimulation with DNP-PPD in the presence of Tbc-primed T cells (cognate interaction). These results indicate that B cells responsible for the cognate interaction and those having TRF acceptor site(s) belong to a distinct subpopulation of B cells, and that the cytocidal action of the noncovalent conjugate of the antibody and RA formed from the biotinylated antibody and avidin-RA via an avidin-biotin complex has immunologic selectivity, eliminating only the latter subset of B cells recognized by the antibody.
We performed angiotension-induced hypertension cancer chemotherapy in a patient with unresectable gastric cancer with invasion to the pancreatic head and lymphatic metastases along the common hepatic and celiac arteries. At re-operation, the tumor size was remarkably decreased and we were able to perform curative subtotal gastrectomy without invasion and metastases. The pathological specimen showed no malignant cells at postoperation.
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Mental symptom is one of the characteristic features in myotonic dystrophy, but documentation of mental signs including pathological changes of the brain has been imprecise. An attempt to show the involvement of the central nervous system by CT scan and EEG has been done in our department. The material consists of 14 patients 10 males and 4 females, from 15 to 50 years of age. CT scan of the 14 patients showed diffuse enlargement of lateral and third ventricles without definite atrophy of cerebral cortex and brainstem. Measurements of various parts of the ventricles showed a difference and an increase with age of values compared with that obtained from 49 neurologically normal persons (P less than 0.01). Main findings of EEG taken from 7 patients were slowing and low voltage of background activity, and 4 patients showed monotonous alpha waves. Both asymmetry and paroxysmal waves were not found. There was no significant correlation between the degree of ventricular enlargement and the frequency of the alpha activity (P greater than 0.05). Our study reveals that the ventricular enlargement is more correlated with aging than the severity of muscle involvement or the degree of mental deterioration. This fact possibly reflects a progressive nature of the pathology of the brain, especially the white matter.
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The pharmacokinetics of human recombinant interferon-beta ( ReIFN -beta) was compared with that of natural human interferon-beta (IFN-beta) in monkeys and rabbits after intravenous or intramuscular injection. After intravenous injection of 10(6) units/kg of ReIFN -beta or IFN-beta into monkeys or rabbits, serum levels of both interferons declined biexponentially. No significant differences between ReIFN -beta and IFN-beta were detected in most pharmacokinetic parameters including T1/2-beta, though T1/2-alpha of ReIFN -beta was significantly shorter than that of IFN-beta. These results seemed to be in conflict with the observed difference of stability of the interferons in vitro since ReIFN -beta was less stable than IFN-beta in monkey and rabbit serum. When ReIFN -beta (10(7) units/kg) was injected intramuscularly into monkeys or rabbits, it remained detectable in the serum for 24 hr; an absorption phase and an elimination phase were seen. However, AUC (the area under the serum concentration curve) after the intramuscular injection of ReIFN -beta was about one-half and one-third of that after the intravenous injection in monkeys and rabbits, respectively. ReIFN -beta and IFN-beta (10(6) units/kg) were both detectable in the serum after intramuscular injection into rabbits, but the level of ReIFN -beta was lower than that of IFN-beta. These results indicate that the lack of carbohydrate in ReIFN -beta did not essentially affect the in vivo pharmacokinetics in monkeys and rabbits after intravenous injection, but this was not the case after intramuscular injection.
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In an attempt to improve the diagnosis and treatment of intracranial metastases of choriocarcinoma, the authors carried out a clinicopathologic investigation of 36 patients with choriocarcinoma metastasized in the brain. Analysis on the autopsy findings of 30 cases with documented intracranial metastases of choriocarcinoma proved neurosurgical resectability in most cases. After initiation of the clinical use of dactinomycin in 1965, 5 of 10 patients in the surgically treated group, and 1 of 17 in the group without surgery, survived for more than 6 months after development of neurologic symptoms. Intracranial metastases of choriocarcinoma should be treated as follows: (1) if symptoms of increased intracranial pressure progress to a life-threatening situation, removal of tumor or, at least, decompression should be immediately performed; (2) multidrug chemotherapy supplemented by whole-brain irradiation should be started within several days after surgery; and (3) if symptoms are not present, chemotherapy combined with irradiation is the first treatment of choice.
In studies of antitumor antibody-cytotoxic agent conjugates as potential antitumor agents with improved tumor specificity, the toxic subunit A-chain of ricin was conjugated with a monoclonal antibody to a tumor-associated antigen expressed weakly on murine leukemia L1210 cells and strongly on L1210/GZL cells, a guanazole-resistant subline of L1210, employing N-succinimidyl 3-(2-pyridyldithio)propionate as cross-linking agent. The conjugate (anti-L1210 conjugate) exhibited a potent concentration-dependent cytotoxicity against cultured L1210/GZL cells, and inhibited cell growth at concentrations over 0.8 micrograms/ml. The conjugate killed all L1210/GZL cells at a concentration of 100 micrograms/ml. Neither nonimmune conjugate similarly prepared from mouse nonimmune IgG nor unconjugated anti-L1210 IgG alone showed cytotoxicity against L1210/GZL cells. When (BALB/c X DBA/2)F1 mice inoculated with 1 X 10(5) L1210/GZL cells were treated with IP injections of 27 micrograms anti-L1210 conjugate 1 h and 5 days after tumor cell inoculation, a life-prolonging effect was observed. [Lifespan in treated animals as percentage of that in controls (T/C) = 146%]. However, when the dose per injection was increased to 50 micrograms per mouse, survival was the same as in the control group. Postmortem examination of mice that had been treated with 50 micrograms anti-L1210 conjugate revealed lesions with necrosis and hemorrhage in the liver parenchyma and the intestinal epithelium, respectively. A similar toxic effect on the host mice was also observed with nonimmune conjugate.
Retinochrome is readily reduced by sodium borohydride into an N-retinyl protein that emits visible fluorescence upon irradiation with near-ultraviolet light. Rhodopsin is also converted to a similar fluorescent product, but only when denatured with formaldehyde before reduction. Based upon this difference, retinochrome was discriminated from rhodopsin on frozen sections. The distribution of these two photopigments in various photosensitive tissues was examined by means of epifluorescence microscopy. In the octopus retina (Octopus vulgaris), the yellow-green fluorescence of reduced retinochrome was observed in both the basal regions of the outer segments and throughout the inner segments of the visual cells, while the fluorescence of reduced rhodopsin was restricted to within the rhabdomal layer of the outer segments. In the squid parolfactory vesicles (Todarodes pacificus), rhodopsin was present in the central lumen, which contains the distal processes of the photoreceptor cells, while retinochrome was detected in the myeloid bodies scattered within the vesicular wall. In the slug retina (Limax flavus), rhodopsin was found in the microvilli, and retinochrome appeared to be concentrated in the photic vesicles of the visual cells.
The configurations of the retinal chromophore in light and dark reactions of squid retinochrome were investigated by means of high-performance liquid chromatography. Orange light isomerized the chromophore of retinochrome, all-trans-retinal, mainly to the 11-cis configuration in metaretinochrome. Irradiation with shorter-wavelength lights not only accelerates the photoreversal of metaretinochrome to retinochrome but also leads to a slight production of isoretinochrome (13-cis-retinochrome), yielding a photoequilibrium mixture of three kinds of retinochrome. 13-cis- and 9-cis-retinochromes are photosensitive, and are converted into metaretinochrome upon irradiation with orange light. When steadily exposed to orange light in the presence of a trace of retinochrome-protein, all of the all-trans-, 13-cis-, and 9-cis-retinals are catalytically isomerized only to the 11-cis form, although the reaction rate is reduced in the order of the retinals listed above. In the dark, 9-cis-retinochrome, like retinochrome, remains unchanged, but both meta- and 13-cis-retinochromes slowly change to retinochrome. The chromophore of 13-cis-retinochrome changes directly to the all-trans form, whereas the 11-cis chromophore of metaretinochrome goes to all-trans mainly through the 13-cis form. The direct isomerization from 11-cis to all-trans hardly occurs at temperatures as low as 20 degrees C, and shows high values of the activation enthalpy and entropy changes. Based upon these findings, the role of retinochrome in the photoreception of the visual cells is discussed.