Biomedical subjects

K Kumaki

Publications and source records attributed to K Kumaki.

At least 37 records · Page 2Linked to original sources

PubMed1995

Molecular cloning and expression of serum calcium-decreasing factor (caldecrin).

We previously reported on the purification of a serum calcium-decreasing factor, referred to as caldecrin, from porcine pancreas, that is thought to be a serine protease (Tomomura, A., Fukushige, T., Noda, T., Noikura, T., and Saheki, T. (1992) FEBS Lett. 301, 277-281). In the present study, we purified caldecrin from rat pancreas and determined its primary structure by cDNA cloning. The predicted caldecrin protein is presumed to be synthesized as a preproenzyme of 268 amino acids with a signal peptide of 16 amino acids and an activation peptide of 13 amino acids, and is, with the exception of a central region, almost identical to the reported rat pancreatic elastase IV sequence. The caldecrin gene is selectively expressed in the pancreas, as judged by Northern blot analysis. After expression in BMT-10 cells, immunoreactive caldecrin was found in the culture supernatant, and it inhibited the parathyroid hormone-stimulated 45Ca release from cultured fetal long bones. Catalytic site mutants were synthesized in a baculovirus system, and recombinant mutants also decreased the serum calcium level of mice. These data implicate caldecrin, a protease closely related to elastase IV, in the regulation of blood calcium levels.

Amino Acid Sequence↗

PubMed1995

Distribution of 1,25-dihydroxyvitamin D3[22-oxa] in vivo receptor binding in adult and developing skin.

Because of the therapeutic potential of oxacalcitriol (OCT, 22-oxa-dihydroxyvitamin D3), in vivo studies were conducted in adult and neonatal rats to identify the nuclear receptor sites of action in different tissues of the skin. Results were compared with those for 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) and oestradiol from previous studies. Autoradiograms were prepared from the dorsal skin of adult rats and the skin of the leg and head regions of neonatal rats 1 or 2 h after the injection of 3H-OCT. Specific nuclear concentrations of radioactivity, eliminated by competition with unlabelled OCT or 1,25(OH)2D3, were found in cells of the epidermis, outer hair sheath, hair bulb and sebaceous glands, but were absent or low in most fibroblasts of the dermis and hypodermis. The strongest nuclear binding of OCT was conspicuous in outer hair sheaths, where it was 1.5 to 3.2 times higher than in keratinocytes of the epidermis. The distribution of nuclear receptors for OCT was similar to that for 1,25(OH)2D3 but in part dissimilar to that for oestradiol. Oestradiol binding was found in the epidermis and hair sheaths, and also predominantly in fibroblasts of the dermis and hair dermal papillae. The results suggest genomic regulatory effects of OCT, similar to the effects of vitamin D, on proliferation, differentiation and activity of keratinocytes, growth and maintenance of hair, and proliferation and secretion of sebaceous glands. This may be utilized therapeutically, since OCT has a lower calcaemic effect than 1,25(OH)2D3.

Animals↗

PubMed1995

[Examination on the courses of the arteries in the axillary region I. The course of the subscapular artery system, especially the relationships between the arteries and the posterior cord of the brachial plexus].

The subscapular artery (Sbs) is the largest and most variable branch of the axillary artery (Ax). Although this Sbs has been defined as a common trunk of the thoracodorsal artery (TD) and the circumflex scapular artery (CS), TD and CS do not always form a common trunk, and the posterior circumflex humeral artery (CHP) is often associated with CS or the CS+TD trunk. Moreover, the subscapular branch (RS) usually arises from CS or CS+TD. Therefore, the subject of the study on Sbs must at least include RS and CHP. However, many anatomical studies on Sbs variation have not included them, and the mechanism causing the variation of Sbs has not been treated except in a few papers. Yamada distinguished two types of subscapular artery in 1967. The first type arose from Ax proximal to the point where Ax passed between the lateral and the medial cord or penetrated the ventral stratum of the brachial plexus. The second type arose from Ax distal to the point. The former type crossed over the medial cord of the plexus to reach the upper lateral thoracic wall, gave off the lateral thoracic artery (TL) and then ran backward on the serratus anterior muscle to reach the deep region of the axilla. Yamada named the former type Sbs "A.subscapularis superficialis" and considered it to be derived from TL. Yamada made an epoch-making report regarding the arteries of the axilla in 1967. He did not, however, refer to the relationship between the arteries to the deep region of the axilla and the posterior cord of the plexus. We called Sbs and the related arteries to the deep region of the axilla "the subscapular artery system" (Sbs system) and examined the courses of the Sbs system in 202 sides of cadavers during the dissecting practices from 1988 to 1992. Our examination revealed that there were three types of Sbs systems, i.e., S-type, I-type, and P-type Sbs systems. The S-type Sbs system was almost the same as Yamada's "A. subscapularis superficialis", branching off from the lateral thoracic artery arising from Ax proximal to the point where Ax penetrated the ventral stratum of the brachial plexus, and ended up in TD or bifurcating into TD and CS. CHP arose from the proximal part of the TD+CS-trunk and ran via the proximal course, or from CS and via the distal course. The S-type CHP ran posterior to the radial nerve (R). The frequency of appearance of the main arteries of the S-type Sbs system decreased sequentially from the medial artery to the lateral one as follows: TD > CS > CHP. Both the I-type and P-type Sbs system arose from Ax distal to the point where Ax penetrated the ventral stratum of the brachial plexus. But the former ran posterior across the medial side of R and the latter ran posterior across the lateral side. The branching point of the I-type Sbs system from Ax was located more proximally than that of P-type. The I-type Sbs system more often gave off CS than TD and CHP. The P-type Sbs system arose from the most distal part of Ax just in front of the lateral axillary hiatus. The sequence of the frequency of appearance was CHP > CS > TD. Both CS and TD of P-type passed behind R. Different types of Sbs systems coexisted. In such cases, the more proximal type gave off more medial arteries and the more distal type gave off more lateral arteries. Exceptions to the rule, for example, coexistence of P-type CS with S-type CHP or I-type TD with S-type CS etc., were never observed. Although different features were distinguished in the stem parts of the three types of Sbs systems, the courses of the peripheral branches of Sbs systems displayed a common pattern on the surface of the subscapular muscle when they were analyzed collectively disregarding the direction of the flow of blood. Therefore, the peripheral part of each Sbs system on the surface of the subscapular muscle was considered to be derived from a common arterial network. In conclusion, the mechanism of the formation of variations in the Sbs system can be understood by the combination

Axillary Artery↗

PubMed1994

Evidence for the uptake of a vitamin D analogue (OCT) by a human carcinoma and its effect of suppressing the transcription of parathyroid hormone-related peptide gene in vivo.

The present study was undertaken to clarify the pharmacokinetics of 22-oxa-1,25-dihydroxyvitamin D3 (22-oxa-1,25-(OH)2D3, OCT), a vitamin D3 analogue with little calcemic activity, and its effect on the transcription of parathyroid hormone-related peptide (PTHRP) gene in nude mice bearing a human carcinoma (FA-6) associated with humoral hypercalcemia. FA-6 tumor expressed vitamin D receptor (VDR) mRNA, and its nuclear extract contained a specific and saturable 1,25-(OH)2D3 binding activity. Although [3H]OCT administered intravenously into FA-6 tumor-bearing nude mice was cleared from the circulation more rapidly than [3H]1,25-(OH)2D3, the uptake of [3H]OCT into the tumor tissue, relative to the radioactivity in the circulation, was greater than that of [3H]1,25-(OH)2D3. Intravenous or oral administration of OCT reduced the steady-state levels of PTHRP mRNA in FA-6 tumor, and nuclear run-off assays demonstrated that the effect of OCT on PTHRP gene expression occurred at a transcriptional level. RNase mapping analysis revealed that both upstream and downstream promoters of the human PTHRP gene were down-regulated by OCT. Finally, OCT exerted a preventive as well as therapeutic effect on cancer-associated hypercalcemia with a marked prolongation of the survival time in tumor-bearing animals. These results suggest that OCT is effectively taken up by a VDR-positive human carcinoma in vivo and has a therapeutic potential for cancer-associated hypercalcemia through suppression of PTHRP gene transcription.

Animals↗

PubMed1994

1,25-Dihydroxyvitamin D3 and 22-oxa-1,25-dihydroxyvitamin D3 in vivo nuclear receptor binding in developing bone during endochondral and intramembranous ossification.

Target cells for 3H-labeled 1 alpha, 25(OH)2 vitamin D3 [1,25(OH)2D3, vitamin D] and its analog 3H-labeled 22-oxa-1 alpha, 25(OH)2 vitamin D3 (OCT) have been identified during endochondral and intramembranous ossification in developing, undecalcified, unembedded bone, using thaw-mount autoradiography. Two-day-old neonatal rats were injected with [3H]1,25(OH)2D3 or [3H]OCT; after 2 h leg, spine, and head were frozen and sectioned. In the epiphyseal-metaphyseal region specific nuclear concentrations of [3H]1,25(OH)2D3 and [3H]OCT were observed in identical cell populations, being low in cells of the articular and resting zone, intermediate in the proliferating zone, and highest in hypertrophic chondrocytes and in osteoblasts and precursor cells. In the primary spongiosa intertrabecular spaces there were a large number of cells with nuclear labeling--probably osteoblasts and precursor cells. In contrast, in the secondary spongiosa intertrabecular spaces, apparent blood-forming cells were mostly unlabeled. Osteoblasts along bone spicules and compact bone in long bones, vertebrae, and head also showed strong nuclear labeling, as did cells of the periosteum. These data suggest that 1,25(OH)2D3 and OCT regulate development, differentiation, and activities of chondrocytes and osteoblasts, including differentiation of resting chondrocytes into proliferating and hypertrophic chondrocytes that involve "chondroclastic" enlargement of lacunae and "trans-differentiation" of surviving hypertrophic chondrocytes; differentiation of stroma cells into osteoblasts; and in periosteum and other regions of intramembranous ossification differentiation of precursor cells and osteoblasts. Nuclear receptor binding and their selective and hierarchical distribution during cell differentiation appear to correspond to multiple genomic effects toward growth, regeneration and repair. The findings indicate a physiological significance and therapeutic potential of 1,25(OH)2D3 and in particular of its less hypercalcemic analog OCT.

Animals↗

PubMed1994

Nerve supply to the accessory soleus muscle.

An accessory soleus muscle was found in the right leg of a cadaver in the dissecting room. This anomalous muscle was situated medially between the distal part of the tibia and the tendo calcaneus. The muscle arose from the anterior aponeurosis of the soleus muscle and was attached with a separate tendon to the calcaneus anteromedial to the tendo calcaneus. The soleus muscle was supplied by two nerves from the tibial nerve. The ramus posterior entered its posterior surface near the proximal border, and the ramus anterior entered the bipenniform part which was located on the anterior aspect of the soleus. One of branches from the r. anterior descended on the surface of the medial half of the bipenniform part and gave off a few twigs for this muscle part. Finally, its terminal entered the accessory soleus muscle and ramified in this muscle. In a teased preparation of the tibial nerve, both the nerve fibres composing this branch to the anomalous muscle and those constituting the r. anterior proper which supplied the bipenniform part were contained in the same funiculus. This mode of nerve supply to the soleus and the accessory soleus muscle suggested that this anomalous muscle derived from the part of the proper soleus muscle supplied by the r. anterior.

Ankle↗

PubMed1993

Soluble interleukin-6 receptor triggers osteoclast formation by interleukin 6.

It has been reported that soluble interleukin (IL)-6 receptor (sIL-6R) is detected in the serum of healthy individuals and its level is increased in patients with multiple myeloma and human immunodeficiency virus infection. Although several reports have suggested that sIL-6R potentiates IL-6 action, its physiological role remains unclear. In this study, we examined the role of sIL-6R on osteoclast formation by IL-6, using a coculture of mouse osteoblasts and bone marrow cells. Neither recombinant mouse IL-6 (mIL-6) nor mouse sIL-6R (smIL-6R) induced osteoclast-like multinucleated cell (MNC) formation when they were added separately. In contrast, simultaneous treatment with mIL-6 and smIL-6R strikingly induced MNC formation. These MNCs satisfied major criteria of authentic osteoclasts, such as tartrate-resistant acid phosphatase (TRAP) activity, calcitonin receptors, and pit formation on dentine slices. The MNC formation induced by mIL-6 and smIL-6R was dose-dependently inhibited by adding monoclonal anti-mouse IL-6R antibody (MR16-1). It is likely that osteoblasts and osteoclast progenitors are capable of transducing a signal from a complex of IL-6 and sIL-6R through gp130, even though they may have no or a very small number of IL-6Rs. Factors such as IL-11, oncostatin M, and leukemia inhibitory factor, which are known to exert their functions through gp130 (the signal-transducing chain of IL-6R), also induced MNC formation in our coculture system. These results suggest that increased circulating or locally produced sIL-6R induces osteoclast formation in the presence of IL-6 mediated by a mechanism involving gp130. This may play an important physiological or pathological role in conditions associated with increased osteoclastic bone resorption.

Animals↗

PubMed1991

Classification of the abdominal splanchnic nerves--a preliminary attempt to re-evaluate their nomenclatures.

The abdominal splanchnic nerves were observed in 22 cadavers (41 sides). The purpose of the study is to give more accurate definition to each nerve, for there are uncertainties in the nomenclature of these nerves. According to PNA, the abdominal splanchnic nerves are classified into three categories, on the basis of their sizes and their levels, namely Nn. splanchnici major, minor, and imus. Although Mitchell (1935) had already claimed that more attention should be given to the levels of ganglia which gave rise to these nerves, no revision has ever been made. Moreover, there still remains the matter of their destinations, which are more significant in defining them. Therefore, in addition to the conventional criteria for the classification, destinations of the nerves were taken into consideration. In the present study, 36 out of 41 sides were grouped into four types according to the said criteria. 5 exceptional cases were interpreted as results of minor modifications of these four types. Naturally, what is important in describing these nerves is to give clear idea about the actual condition of them. It is expected to give more reasonable nomenclature to these nerves based on the present result.

Abdomen↗

PubMed1987

Aberrant course of the left gastric vein in the human. Possibility of a persistent left portal vein.

Two livers with an aberrant course of the left gastric vein were found in 245 Japanese cadavers. The left gastric vein collects branches from the lesser curvature of the stomach, enters the left side of the hepatogastric ligament from the cardiac region and runs towards the left side of hepatic hilus. The vein enters the liver at the left side and joins an intrahepatic branch ramified from the portal vein.

Humans↗

PubMed1982

Plasma Aluminum levels of patients on long term sucralfate therapy.

Plasma aluminum levels of 17 patients with gastric and/or duodenal ulcers who had received four grams of sucralfate daily for eight to ten weeks were compared with those of six control subjects. Aluminum levels were determined by flameless atomic absorption spectrometry. Plasma of patients on long term sucralfate therapy contained 8.41 +/- 6.00 (SD) micrograms aluminum per liter and was not significantly different than that of the control subjects which contained 6.50 +/- 7.87 micrograms per liter. These values agreed well with normal values reported previously. In conclusion, long term ingestion of sucralfate in therapeutic doses does not result in an increase in plasma aluminum concentration.

Aluminum↗

PubMed1978