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Biomedical subjects

T Hirota

Publications and source records attributed to T Hirota.

At least 181 records · Page 10Linked to original sources

Satellited chromosome 9 in a boy with multiple anomalies.

A 5-year-old boy with multiple congenital anomalies showed a satellited long-arm chromosome 9, a previously undescribed abnormality. Various banding analyses of his chromosomes and those of his parents indicated that a reciprocal translocation, t(9;22)(q34.3;q11.21), occurred in the father's gonad, and one of the translocation chromosomes was then transmitted to the patient. Thus, the patient's karyotype was interpreted as 46,XY,-9,+psudic(9),t(9;22)(q34.3;q11.21). He showed several features similar to those of the Williams syndrome. The gene(s) responsible for the syndrome thus could be at either 9q34.3-qter or 22pter-q11.2. Southern blot analysis of the patient's DNA indicated the presence of two copies of the argininosuccinate synthetase gene which had been assigned to 9q34.1-qter. In view of the fact that the 9q34.3-qter segment is monosomic in the patient, the gene locus was deduced to be at 9q34.1-q34.2 segment.

Abnormalities, Multiple↗

Histochemical analysis of the chemical structure of blood group-related carbohydrate chains in serous cells of human submandibular glands using lectin staining and glycosidase digestion.

Using lectin staining methods in combination with exo- and endo-glycosidase digestion procedures, we analyzed the chemical structure of different types of blood group-related substances in serous cells of formalin-fixed, paraffin-embedded human submandibular glands. Serous cells produced only H antigen; A and B antigens were not present, and the expression of H antigen is dependent on the secretor status of the tissue donor. Although reactivity with Ulex europaeus agglutinin I (UEA-I) was not markedly reduced by alpha-L-fucosidase digestion, an affinity for peanut agglutinin (PNA) was seen after fucosidase digestion in the cells from secretors. In those from nonsecretors, no PNA reactivity appeared after enzyme digestion. On the other hand, sialidase digestion elicited PNA reactivity in serous cells irrespective of the donor's secretor status. PNA reactivity observed after fucosidase or sialidase digestion was susceptible to endo-alpha-N-acetylgalactosaminidase (endo-GalNAc-dase) digestion. SBA reactivity in UEA-I-negative cells from secretors, or in cells from fetuses and newborn infants, was markedly reduced by beta-galactosidase digestion. After galactosidase digestion, reactivity with Griffonia simplicifolia agglutinin II (GSA-II) appeared in the corresponding cells. This GSA-II reactivity was almost completely eliminated by subsequent beta-N-acetylhexosaminidase digestion. Whereas PNA reactivity in these cells was not reduced by beta-galactosidase treatment, it was significantly diminished by endo-GalNAc-dase digestion. These results suggest that at least two kinds of precursor disaccharides are produced in submandibular serous cells, i.e., SBA-reactive D-galactose-(beta 1-3,4)-N-acetyl-D-glucosamine and PNA-reactive D-galactose-(beta 1-3)-N-acetyl-D-galactosamine alpha 1-serine or threonine (O-glycosidically linked Type 3 chain or T antigen). Final fucosylation and synthesis of these two types of precursor chain appear to be under the control of the secretor gene.

ABO Blood-Group System↗

Studies on orally active cephalosporin esters. IV. Effect of the C-3 substituent of cephalosporin on the gastrointestinal absorption in mice.

The effect of the C-3 substituent on the oral absorbability of pivaloyloxymethyl (POM) ester of cephalosporin in mice is described. The C-3 substituent affects the physicochemical and biochemical properties of POM ester, such as lipophilicity, water solubility, chemical stability and enzymatic stability. Quantitative analyses of the relationships between these properties and the oral bioavailability have been attempted. Lipophilicity made a parabolic contribution to the absorption. The optimum log P octanol/water value was estimated to be around 2.22. The chemical isomerization of the cephem double bond from delta 3 to delta 2 in the intestinal lumen prior to absorption contributed linearly to decrease of absorption. In the case of POM ester having a larger isomerization rate, more delta 2 isomer was detected in feces and urine. Enzymatic hydrolysis of POM ester to the parent acid in intestinal tissue was faster for a more lipophilic ester. Hydrolytic activity, which was detected in the content of the intestinal lumen, would lower the absorption. The effect of the C-3 substituent on water solubility was not important for the absorption of cephalosporin employed in the present study. Isomerization of the double bond, which was found to be characteristic for cephalosporin ester, presented a problem in the prodrug approach for oral use.

Animals↗

A rare case of asynchronous bilateral B-cell lymphoma of the breast.

We report an asynchronous bilateral malignant lymphoma of the breast, in a 56-year-old woman, presenting unusual clinical signs and histological features. The patient, who had a family history of breast cancer, had undergone a standard right radical mastectomy four years previously for a non-epithelial malignant tumor. At that time, the tumor was thought to be a stromal sarcoma, because some of the neoplastic cells were elongated or vacuolated. The patient recently became aware of a rapidly growing tumor of the left nipple without erosion or pain. This tumor underwent biopsy, and the histological examination showed a non-Hodgkin's lymphoma of diffuse mixed type. Staging procedures demonstrated no sign of generalized disease. Following a modified left radical mastectomy for optimal local control and accurate staging, adjuvant chemotherapy consisting of vincristine, cyclophosphamide, prednisolone and doxorubicin was initiated. Immunohistochemical staining for PAN-B and leucocyte common antigen revealed both tumors to be malignant lymphomas of B-cell type, and the first lymphoma of the right breast was thought to be showing 'signet ring' cell change. Since the two tumors were morphologically quite different from each other, it was suggested that they were asynchronous bilateral primary malignant lymphomas; however, the possibility remains that the recent left breast tumor is a recurrence of the malignant lymphoma of the right breast. The patient is currently disease-free, 10 months after surgery.

B-Lymphocytes↗

[A case of retrograde amnesia of 22 years, continued for 4 days following a general anesthesia accompanied by a permanent amnesia of these 4 days after the complete recovery from the retrograde amnesia].

A case of global amnesia which continued for 4 days following a general anesthesia and recovered without any neurological deficits was reported. The patient was a 38-year-old woman suspected of lung cancer, and scheduled for pulmonary lobectomy. She had a history of appendectomy under spinal anesthesia 22 years before. She was premedicated with diazepam (10mg), atropine (0.5mg) and pentazocine (30mg). Anesthesia was induced with thiamylal (500mg) and succinylcholine (140mg) iv and 100% oxygen. Anesthesia was maintained with enflurane and nitrous oxide with oxygen for 3 hours. After her recovery from anesthesia, a retrograde amnesia of 22 years was observed and continued for 4 days. Then the memory was restored completely, but the amnesia during these 4 postoperative days remained permanently. We have documented the case of amnesia in the immediate postoperative period which is similar to transient global amnesia. It seems likely that this amnesia was caused by drug interaction, hypoxia, decreased cerebral perfusion or psychogenic effects of general anesthesia.

Adult↗

Prognostic contributions of Helix pomatia and carcinoembryonic antigen staining using histochemical techniques in breast carcinomas.

Helix Pomatia (HPA) and carcinoembryonic antigen (CEA) staining were studied in 113 primary breast carcinomas, 63 metastatic lymph nodes and 10 resected local recurrences, using the avidin-biotin-peroxidase complex (ABC) method. Positive percentage rates were 41 (46/113) for HPA and 24 (27/113) for CEA in primary tumors, and 80 (8/10) for HPA but only 10 (1/10) for CEA in metastatic lesions. HPA staining showed a statistically significant correlation with negative estrogen receptor (ER) status (r -0.25, P = 0.05) and high nuclear grade (r 0.20, P = 0.04). Cancers with positive HPA staining were associated with a lower survival rate than those without (P = 0.0001), irrespective of menopausal status. CEA staining showed a marginal correlation with survival (P = 0.06: log rank test). The five-year survival rate of 21 cases positive for these two markers was only 5%. Multivariate analysis revealed HPA staining to be the best prognostic factor. The data indicated that HPA staining might be a valuable prognostic factor for breast cancer patients, especially when combined with CEA staining.

Breast Neoplasms↗

[Changing trends in the surgical management of breast carcinoma in Japan].

Modified mastectomy, which involved removal of the breast, overlying skin and axillary contents but spares the pectoralis muscle, has recently been established as an entirely satisfactory approach for Stage I and Stage II breast carcinoma. In a sequential series of patients, we noted that the traditional mastectomy followed by radiation to axilla and adjacent area failed to confirm the efficacy to support the prevention for local relapse in the past decade. The concepts of adjuvant chemotherapy evolved primarily from clinical trials: CMF and CAMF have been shown to influence favorably the therapy of premenopausal women with positive. nodes. Additional endocrine adjuvant treatment in postmenopausal women with positive nodes was significantly superior to that with CAMF. Immediate breast reconstruction following modified mastectomy or subcutaneous mastectomy was safe, simple, and possible to produce the patient's satisfaction. There was a positive effect on life style and on sexual, social or work relationships. Finally, in recent years, several studies have reported that more conservative treatment, such as partial mastectomy and nodes dissection with postsurgical radiotherapy are as effective as modified mastectomy. Present research will likely continue to modified current treatment as more data are gathered and analyzed clinically and histologically.

Adult↗

[Mercury in hair of patients with ALS].

In middle of Kii peninsula, one of the biggest mercury mine in Japan had been present until about 10 years ago. The mercury contents in water and fish are reported to be higher in this district. So we investigated the mercury in hair of patients and normal controls. In this study the subjects are 23 cases of ALS including 15 cases in Nara and Mie and 8 cases in other prefectures except in Kii peninsula, 14 cases with ataxia, 11 cases with other degenerative diseases like Parkinson's disease and Alzheimer's disease, 25 cases of cerebrovascular disease as compared to 26 normal controls. The hair are taken from 3 areas on head of patients and normal controls. They are washed in 2% sodium lauryl sulfate and stirred in distilled water several times, and they are soaked in acetone and dried in filter paper. They are inserted in fire and vaporized mercury are measured (Zeeman Effect Mercury Analyzer) in ppm. The hair mercury concentration is 2.81 ppm in ALS in total, 3.62 ppm in ALS in Nara and Mie and 1.39 ppm in outside of Kii Peninsula, 2.34 ppm in ataxia, 1.83 ppm in other degenerative diseases, 1.66 ppm in cerebrovascular disease and 1.44 ppm in normal controls. Statistically it is significant (p less than 0.05) between that in ALS in Nara and Mie and that in normal controls. 6 cases (40%) with ALS in Nara and Mie have the value above the mean +2 standard deviation of controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Action mechanism of amphipathic peptides gramicidin S and melittin on erythrocyte membrane.

Amphipathic peptides gramicidin S and melittin caused a characteristic colloid-osmotic hemolysis on human erythrocytes; that is, the peptides produced initially a small membrane lesion in erythrocyte membrane, followed by the release of hemoglobin. The size of membrane lesion increased with an increase in the concentration of peptide. Under the conditions causing membrane lesion, we observed the release of membrane fragments containing phospholipids. The present results show that both the peptides have the ability to stimulate the release of membrane fragments out of the cells and this brings about the perforation of molecules of small size, leading to a colloid-osmotic hemolysis.

Amino Acid Sequence↗

Effects of alpha-galactosidase digestion on lectin staining in human pancreas.

Effects of alpha-galactosidase (from green coffee beans) digestion on lectin staining were examined in formalin-fixed, paraffin-embedded human pancreatic tissues from individuals of blood-group B and AB. Digestion with the enzyme resulted in almost complete loss of Griffonia simplicifolia agglutinin I-B4 (GSAI-B4) staining in the acinar cells with concomitant appearance of Ulex europaeus agglutinin-I(UEA-I) staining in the corresponding cells. In addition, reactivity with soybean agglutinin(SBA) was also imparted by the enzyme digestion in GSAI-B4 positive acinar cells. beta-Galactosidase digestion following alpha-galactosidase digestion neither reduced the reactivity with SBA nor induced the reactivity with Griffonia simplicifolia agglutinin-II(GSA-II) in GSAI-B4 positive cells, while in UEA-I positive cells, both reduction of SBA reactivity and appearance of GSA-II reactivity occurred after simple beta-galactosidase digestion as well as sequential digestion with alpha- and beta-galactosidase. However, when alpha-L-fucosidase digestion procedure was inserted between alpha- and beta-galactosidase digestion, UEA-I staining imparted by alpha-galactosidase digestion was markedly decreased in intensity and GSA-II reactivity was appeared in GSAI-B4 positive acinar cells. Furthermore, after sequential digestion with alpha-galactosidase and fucosidase, reactivity with peanut agglutinin(PNA) was revealed in GSAI-B4 positive acinar cells as well as UEA-I positive cells in secretors. In non-secretors, strong PNA staining was usually observed in the acinar cells throughout the glands without enzyme digestion.(ABSTRACT TRUNCATED AT 250 WORDS)

ABO Blood-Group System↗

Cytochemical localization of blood group substances in human salivary glands using lectin-gold complexes.

We investigated localization of blood group antigens and their related substances in human labial salivary and submandibular glands by application of a post-embedding cytochemical staining procedure using lectin- or glycoprotein-gold complexes. Surgical tissue was obtained from 10 patients. Blood group-specific lectins, such as Dolichos biflorus agglutinin or Helix pomatia agglutinin (group A-specific), Griffonia simplicifolia agglutinin-I B4 (group B-specific), and Ulex europaeus agglutinin I (group H-specific) could recognize A, B, and H antigens, respectively, only in mature secretory granules (mature SG), which were found preferentially in cells in the late phase of the maturation cycle. In immature secretory granules (immature SG), which were found in cells in the early or middle phase of the maturation cycle, no binding with these lectins was observed. The Golgi complexes and endoplasmic reticula also were not labeled with these lectins. In blood group O and B secretors, blood group antigens were uniformly distributed throughout all the mature SG examined. However, in blood group A secretors, the distribution was heterogeneous, i.e., in some granules only H antigen was demonstrated, whereas in others both A antigens and a small amount of H antigens were detected. Among the blood group-nonspecific lectins, wheat germ agglutinin (WGA) was found to bind more preferentially to immature SG than to mature SG. This was demonstrated irrespective of the blood group and secretor status of the tissue donor, except that in blood group A secretors WGA bound strongly to some mature SG which possessed A antigen. We discuss the significance of cellular and subcellular mosaic distribution of blood group antigens in connection with morphological differences of secretory granules and the maturation cycle of mucous cells.

ABO Blood-Group System↗

Effects of alpha-L-fucosidase digestion on lectin staining in human pancreas.

We examined the effects of alpha-L-fucosidase digestion on lectin staining in formalin-fixed, paraffin-embedded human pancreatic tissue from individuals of different blood groups. Digestion with the enzyme resulted in apparent diminished intensity of Ulex europaeus agglutinin-I (UEA-I) staining in the acinar cells. In addition to the decreased intensity of UEA-I staining, reactivity with soybean agglutinin (SBA) was increased in the enzyme-susceptible, UEA-I-reactive cells. The intensity of Griffonia simplicifolia agglutinin-II (GSA-II) staining performed after beta-galactosidase digestion in UEA-I-reactive acinar cells was markedly increased by prior treatment with fucosidase. GSA-II staining following sequential digestion with fucosidase and galactosidase was completely abolished by subsequent digestion with beta-N-acetylhexosaminidase. These results therefore substantiate the previous assumption that SBA-reactive D-galactose-(beta 1-3,4)-N-acetyl-D-glucosamine and GSA-II reactive beta-N-acetyl-D-glucosamine imparted following galactosidase digestion represent precursors of H antigen. The present study further demonstrated that intense peanut agglutinin (PNA) staining was imparted after digestion with fucosidase in UEA-I-reactive sites in secretors. In contrast, nonsecretors showed vivid PNA staining that was usually detected throughout the pancreas without prior enzyme digestion. Here, fucosidase digestion had if any little effect on PNA staining. These results suggest that in secretors a terminal trisaccharide, fucosylated D-galactose-(beta 1-3)-N-acetyl-D-galactosamine exhibiting positive PNA reaction after fucosidase digestion, exists in UEA-I-reactive acinar cells. It is assumed that the secretor gene could control the step of final fucosylation of D-galactose-(beta 1-3)-N-acetyl-D-galactosamine in human pancreas.

Adolescent↗

[Five-week subacute intravenous toxicity study of cefodizime sodium in dogs].

A subacute toxicity study of cefodizime sodium (THR-221), a new cephem antibiotics, was carried out using male and female beagle dogs. THR-221 was intravenously administered to the dog at dose levels of 500, 1000 and 2000 mg/kg/day for 5 weeks, followed by 4 weeks recovery period. Cefotetan (CTT) as a reference drug was administered in the same manner at a dose level of 2000 mg/kg/day. The summarized results obtained are as follows: 1. Vomiting and salivation were observed in dogs given 1000 and 2000 mg/kg/day of THR-221. However, it caused no deaths or significant effects on body weight and food consumption in all groups treated with THR-221. 2. No toxicological changes associated with the administration of THR-221 were found in urinary and hematological examinations. 3. In serum biochemical examinations, increase or tendencies of increase of albumin and A/G ratio, probably due to the antibacterial action of THR-221, were detected at all dose levels of THR-221. 4. There were no dose-related changes in hepatic and renal function, fecal occult blood, ophthalmological, electrocardiographic and auditory examinations, absolute and relative organ weights. 5. Histopathological examinations revealed fibrosis or granulation in perivascular area of injection sites, particularly in males given 2000 mg/kg/day of THR-221. 6. After 4 weeks of recovery period, above-mentioned changes were generally disappeared and it was suggested that these were reversible ones. 7. In groups treated with CTT (2000 mg/kg/day), damages were recognized mainly in erythron values, liver and kidney, as compared with the same dose of THR-221. Therefore the toxicity of THR-221 was less than that of CTT. 8. From these results, the non toxic effective dose level and the toxic dose level of THR-221 were estimated to be 500 mg/kg/day and more than 2000 mg/kg/day respectively, for male and female dogs.

Animals↗

Synthesis and mutagenicity of a ring-A-aromatized bile acid, 3-hydroxy-19-nor-1,3,5(10)-cholatrien-24-oic acid.

It has been presumed that ring-A-aromatized bile acids are produced from biliary bile acids by intestinal flora and the acids thus formed participate in the large bowel carcinogenesis. One of these acids is probably 3-hydroxy-19-nor-1,3,5(10)-cholatrien-24-oic acid, judged from the literatures. Consequently, this acid was synthesized from previously prepared 3-methoxy-19-nor-1,3,5(10)-cholatrien-24-ol. The phenolic ether was successively oxidized with pyridinium chlorochromate and wet silver oxide to give 3-methoxy-19-nor-1,3,5(10)-cholatrien-24-oic acid in high yield, which, after successive treatments with methanol containing a catalytic amount of p-toluenesulfonic acid, a combination of aluminum chloride and ethanethiol, and alkali, gave the desired compound in satisfactory yield. The compound was not mutagenic in Salmonella tester strains TA 98 and TA 100, but it increased the mutagenicity of 2-aminoanthracene when both were applied to plates together. When compared with cholic, deoxycholic, and lithocholic acids, the investigated compound exhibited about two to threefold increase of mutagenicity in the latter assay.

Bile Acids and Salts↗

Physico-chemical properties of muroctasin.

N2-[(N-acetylmuramoyl)-L-alanyl-D-isoglutaminyl-N6-stearoyl-L-lysine (MDP-Lys(L18), muroctasin) was studied to clarify its chemical structure and physico-chemical properties. The chemical structure of MDP-Lys(L18) was confirmed by UV, IR, NMR and MS analyses as well as by elemental analysis. The physico-chemical properties were investigated by thermal analysis, powder X-ray analysis, ionization constant measurement, high-performance liquid and thin-layer chromatography.

Acetylmuramyl-Alanyl-Isoglutamine↗

Studies on the stability of muroctasin and degradation products built under extreme conditions.

Decomposition of N2-[(N-acetylmuramoyl)-L-alanyl-D-isoglutaminyl]-N6-stearoyl-L-lysine (MDP-Lys(L18), muroctasin) under extreme conditions was investigated. MDP-Lys(L18) in an aqueous solution was heated under reflux for 4 h to give the decomposition products D-1, D-2, D-3 and D-4. Reaction of MDP-Lys(L18) with 0.1N NaOH at room temperature for 5 h gave D-1, and that with 1 N HCl under reflux for 1 h afforded D-4. MDP-Lys(L18) was found to be stable to light and heat. MDP-Lys(L18) in a powder form was stored at room temperature or at 25 degrees C and 75% relative humidity for 3 days to 18 months. Quantitative analysis, thin-layer chromatography, and tests for appearance and color change, etc., were performed in the stored samples. MDP-Lys(L18) was found to be stable, but hygroscopic.

Acetylmuramyl-Alanyl-Isoglutamine↗