Ultrasound-guided intralesional laser treatment of venous malformation in the oral cavity.

An ultrasound-guided intralesional photocoagulation (ILP) technique using a laser is described for treatment of deep venous malformations in the oral cavity. ILP is basically a blind operation and has a risk of unintended destruction of surrounding normal tissue, therefore the authors now routinely use guidance by ultrasonography using a mini-probe to improve the safety and reliability of ILP. This approach enables safe fibre insertion, appropriate laser irradiation, and intraoperative assessment of coagulation. The use of this technique is described in 8 patients. The authors conclude that ultrasound-guided ILP with a laser is a promising technique for less-invasive treatment of a vascular malformation in the oral cavity.

[Treatment outcomes with vinorelbine for metastatic breast cancer patients previously treated with both doxorubicin and docetaxel].

The purpose of this study was to evaluate the efficacy and toxicity of weekly vinorelbine (VNB) in patients with metastatic breast cancer previously treated with both adriamycin (ADM) and docetaxel (TXT). VNB was administered weekly at the dose 20 mg/m2 by i.v. infusion over 20 minutes followed by flushing the vein with 100 ml of normal saline. From June 1999 to August 2000, ten patients were enrolled in this study. Patient characteristics were that the cumulative doses (median) of previous ADM and TXT were 300 mg (range, 120-880 mg), 560 mg (range, 120-960 mg) respectively. The median number of metastatic sites was four, with poor performance status (ECOG 1-2: 40%, 3-4: 60%). The median cycles of weekly VNB were seven (range: 2-12). Two of 10 assessable patients obtained partial response, with an overall response rate of 20%. The main toxicity (NCI grade 4) was leukopenia in 10% of 10 patients. Phlebitis (grade 2) was observed in 4 of 10 patients (40%). VNB is an active agent against metastatic breast cancer pretreated with both ADM and TXT, possessing no severe toxicities.

Role of cortical tumour-suppressor proteins in asymmetric division of Drosophila neuroblast.

Cellular diversity during development arises in part from asymmetric divisions, which generate two distinct cells by transmitting localized determinants from a progenitor cell into one daughter cell. In Drosophila, neuroblasts undergo typical asymmetric divisions to produce another neuroblast and a ganglion mother cell. At mitosis, neural fate determinants, including Prospero and Numb, localize to the basal cortex, from which the ganglion mother cell buds off; Inscuteable and Bazooka, which regulate spindle orientation, localize apically. Here we show that a tumour-suppressor protein, Lethal giant larvae (Lgl), is essential for asymmetric cortical localization of all basal determinants in mitotic neuroblasts, and is therefore indispensable for neural fate decisions. Lgl, which itself is uniformly cortical, interacts with several types of Myosin to localize the determinants. Another tumour-suppressor protein, Lethal discs large (Dlg), participates in this process by regulating the localization of Lgl. The localization of the apical components is unaffected in lgl or dlg mutants. Thus, Lgl and Dlg act in a common process that differentially mediates cortical protein targeting in mitotic neuroblasts, and that creates intrinsic differences between daughter cells.

miranda localizes staufen and prospero asymmetrically in mitotic neuroblasts and epithelial cells in early Drosophila embryogenesis.

When neuroblasts divide, prospero protein and mRNA segregate asymmetrically into the daughter neuroblast and sibling ganglion mother cell. miranda is known to localize prospero protein to the basal cell cortex of neuroblasts while the staufen RNA-binding protein mediates prospero mRNA localization. Here we show that miranda is required for asymmetric staufen localization in neuroblasts. Analyses using miranda mutants reveal that prospero and staufen interact with miranda under the same cell-cycle-dependent control. miranda thus acts to partition both prospero protein and mRNA. Furthermore, miranda localizes prospero and staufen to the basolateral cortex in dividing epithelial cells, which express the three proteins prior to neurogenesis. Our observations suggest that the epithelial cell and neuroblast (both of epithelial origin) share the same molecular machinery for creating cellular asymmetry.

Clinicopathological characteristics of stage 1 gastric cancer: comparison of macroscopic and microscopic findings.

BACKGROUND/AIMS: Laparoscopic surgery or endoscopic mucosal resection for early stages of gastric cancer have been introduced recently in many regions. In such cases, a precise diagnosis is needed prior to treatment, since understaging of gastric cancer may lead to treatment failure and impairment of curability and prognosis. The clinicopathological features of understaged cases in macroscopic Stage 1 gastric cancer have not been clarified yet. MATERIAL AND METHODS: We examined 435 patients with intra-operative findings of macroscopic Stage 1 gastric cancer and compared clinicopathological features of 354 patients (Group A) with both macroscopic and histological stage 1 cancer and 81 patients (Group B) with macroscopic Stage 1 but histologically proven to be more advanced cancer. RESULTS: Among 435 patients with macroscopic Stage 1, there were 81 (18.6%) with histologically more advanced stages (44 of stage 2, 34 of stage 3, and 3 of stage 4). There were no statistical differences in age, sex, operative procedure, and extend of lymph node dissection between the groups. Carcinomas in the 81 Group B patients tended to have larger tumors (> 4 cm), located in the middle third and along the lesser curvature of the stomach, appeared to be Borrmann V type (unclassified type) and were histologically more often associated with undifferentiated type, INF-gamma, lymphovascular invasion, lymph node metastasis, and invasion into a layer deeper than submucosa, all of which resulted in significantly poorer prognosis. CONCLUSIONS: Pre-operative and intra-operative assessment of the stage for gastric cancer was not always accurate enough and about one fifth cases with macroscopic Stage 1 gastric cancer were understaged. Thus, we recommend gastrectomy plus radical lymphadenectomy (at least D2) for the treatment of choice, from the points of view of curability and prognosis when gastric carcinoma is associated with the above mentioned characteristics.

Stimulatory factors for enzymatic biotin synthesis from dethiobiotin in cell-free extracts of Escherichia coli.

The activity of biotin synthesis from dethiobiotin was found in cell-free extracts of an Escherichia coli bioB transformant. Among the sulfur compounds tested, only S-adenosyl-L-methionine (AdoMet) had a significant effect, while methionine and cysteine were inert. The activity was linearly stimulated by increasing protein concentration. When the dialyzed cell-free extracts were used for the reaction, NADP+, NADPH, and FAD among the well-known cofactors tested promoted the activity. Furthermore, in the presence of AdoMet, cysteine was apparently effective for biotin synthetic activity.

[Pharmacological study of 5'-DFUR oral administration and the clinical responses against gastrointestinal carcinoma].

In 4 out of 5 patients given 400 mg orally 5'-DFUR before surgery, intratumor 5-FU concentration showed over 150 ng/g. The concentration of either 5-FU or 5'-DFUR in the portal and peripheral blood of these patients exceeded the limits of assay. 5-FU concentration in peripheral blood was less than 0.05 micrograms/ml. White blood cell and platelet counts in the patients given 1,600 mg/day (no administration for 2 days/week) of 5'-DFUR for one month were essentially the same with those at the time of start of the treatment. Two of three patients showed minor response following the treatment with 5'-DFUR. Thus, administration of 1,600 mg/day of 5'-DFUR may be considered as an effective treatment of fluopyrimidine against advanced cancer. For the prediction of gastrointestinal side effect, assay of the 5-FU concentration in the portal blood seemed to be useful.

Enzymatic conversion of dethiobiotin to biotin in cell-free extracts of a Bacillus sphaericus bioB transformant.

The activity of biotin synthase, responsible for biotin synthesis from dethiobiotin, was demonstrated in a completely defined reaction mixture with cell-free extracts of a Bacillus sphaericus bioB transformant. Among the sulfur compounds tested, only S-adenosyl-L-methionine was active, while L-methionine and L-cysteine had no significant effect. Protein concentrations higher than 15 mg/ml in the reaction mixture were needed to detect biotin synthase activity. When dialyzed cell-free extracts were used for the reaction, NADH, NADPH, or FAD among the well-known cofactors tested enhanced the activity, and Fe2+, Mn2+, and Ca2+ among the metal ions tested also had some effects.

On the mechanism of biotin synthase of Bacillus sphaericus.

A cell-free system of a bioB transformant of Bacillus sphaericus, effecting the last step of biotin biosynthesis, namely the introduction of sulfur into dethiobiotin has been recently described. S-adenosyl methionine (SAM) is absolutely necessary for activity. We show here, through experiments with [35S]SAM and [35S]Cys, that the sulfur donor is not SAM but probably cysteine (Cys) or a derivative. This finding together with the fact that NADPH and FAD are required for activity leads us to postulate some analogy between the biotin synthase system and other systems which use SAM as a source of desoxyadenosyl radical.

Laser applications in plastic and reconstructive surgery.

Very shortly after the laser's first successful firing in 1960, applications were found in the medical field in the specialities of ophthalmology and dermatology and have since expanded to include indications in plastic and reconstructive surgery. In the photodestructive mode, laser energy is used selectively to vaporize, incise, excise, ablade and coagulate target tissue; the surgical laser can also degrade or denature protein in the target tissue, and the latter photoreaction now forms the basis for laser tissue welding in a variety of tissue types. The author refers to these photodestructive applications as high reactive-level laser treatment, or HLLT. In laser therapeutic applications, the temperature of the cells may rise only very slightly or not at all, and there is no immediate irreversible change in the target tissue architecture. The level of reaction is thus lower than the cell survival threshold, giving a direct photoactivative effect. The author refers to this as low reactive-level laser therapy, or LLLT: LLLT applications include pain attenuation, wound healing acceleration; enhanced remodeling in accelerated bone and tendon repair; restoration of normal neural function; normalization of abnormal hormonal function; modulation of the autoimmune system; control of hyper- and hypotension and so on. HLLT and LLLT are contrasted and compared, and applications of both HLLT and LLLT in PRS are discussed in brief.

Development of low reactive-level laser therapy and its present status.

A new subspecialty in the medical application of the laser has developed, especially over the last decade, depending on the therapeutic rather than the surgical applications of the laser. Laser therapy, or preferably, Low reactive-Level Laser Therapy (LLLT) is now being recognized as a valid medical tool. Two types of LLLT are presented, simultaneous and pure. In surgical laser applications, ranges of heat are generated in the target tissue, destroying or altering its architecture. This is referred to as high reactive-level laser treatment, or HLLT. In addition, nonphotothermally destructive reactions may also occur, such as photo-osmosis. These are also part of HLLT. Simultaneously, nondestructive thermal and nonthermal bioactivation occur at the periphery of the target tissue: this is "simultaneous LLLT" and occurs along with HLLT, explaining some of the advantages of laser surgery. Laser systems have been developed which deliver power and energy densities below the destructive level, only to activate the irradiated tissue. This is "pure LLLT." The history and background of LLLT are presented, the terminology discussed, and practical applications of LLLT are presented.

Appraisal of myocutaneous flapping for treatment of postmastectomy lymphedema. Case report.

Two patients with severe postmastectomy lymphedema of the upper extremity were treated with myocutaneous flapping, using latissimus dorsi muscle. Complete disappearance of edema was achieved by 11 months postoperatively in one case and 50% reduction by 8 months in the other case. The satisfactory results commend the procedure, which has yet to gain global acceptance.

Elucidation of calpain dependent phosphorylation of myosin light chain in human platelets.

Newly synthetized calpain inhibitors (CI-I approximately III) were used to prove potential participation of calpain in protein phosphorylation. CIs were about 1,000 times more potent against platelet calpain I than N-ethyl-maleimide (NEM) and an epoxy succinate derivative (E-64). CI-II inhibited 20K (myosin light chain) and 47K phosphorylation of Ca2+-stimulated lysed platelets as well as protein degradation (actin binding protein, P235). Both myosin light chain kinase (MLCK) and C-kinase dependent phosphorylation of 20K were inhibited by CI-II as demonstrated in phosphopeptides mapping. Electropermeabilized platelets (EP) were employed to examine the effects of CI-II on Ca2+ mediated reactions in non-lysed platelets. Phosphorylation of 20K and 47K induced by Ca2+ addition to EP was inhibited by CI-II, though secretory response was not modified. Only MLCK dependent phosphorylation of 20K was observed in Ca2+-activated EP, which was inhibited by CI-II. Collectively, the data indicated that calpain may activate both MLCK and C-kinase to phosphorylate 20K by partial proteolysis.

Mechanism of the haemostatic effect of ethanolamine oleate in the injection sclerotherapy for oesophageal varices.

Changes in coagulation and fibrinolysis were investigated in 20 patients with oesophageal varices, who underwent endoscopic injection sclerotherapy (EIS) with 5 per cent ethanolamine oleate (EO), by means of serial determination of plasma fibrinopeptide A (FPA) and fibrinopeptide B beta 15-42 (B beta 15-42). One hour after the completion of EIS, the value of FPA was significantly increased to 38.1 +/- 11.1 ng/ml (mean +/- s.e.m.) from a pre-EIS value of 7.1 +/- 1.4 ng/ml (P less than 0.01) and it gradually returned to normal range by 48 h after EIS. A very similar change was observed in the value of B beta 15-42 (P less than 0.01). These observations indicated that EIS provokes transient activation of coagulation and fibrinolysis. In vitro studies, however, revealed that EO inhibits fibrin clot formation because of the Ca2+-chelating ability of its constituent ethanolamine, although oleate or benzyl alcohol exhibited procoagulant activity in FPA formation in vitro. Nevertheless, an external application of EO or oleate over decapsulized kidney of rat resulted in a significant accumulation of 125I-labelled fibrin(ogen). From these results it was suggested that intravascular injection of EO, which exerts an inhibitory effect on coagulation in vitro, activates the local coagulation system. The activation may be accelerated by an acute inflammatory process provoked by oleate, which is supported by such clinical manifestations as mild fever, retrosternal pain leukocytosis and an increase in plasma fibrinogen level which was observed in all during the period.

Possible participation of calpain in myosin light chain phosphorylation of human platelets.

We previously demonstrated that myosin light chain kinase (MLCK) of gizzard is proteolyzed by platelet calpain. It has been also reported that partially cleaved MLCK may phosphorylate myosin light chain (20K) in the absence of calmodulin. Therefore, a possible participation of calpain in 20K phosphorylation was studied in human platelets, utilizing various inhibitors. An epoxy succinate derivative (E-64) or N-ethylmaleimide (NEM), used as calpain antagonist, inhibited 20K phosphorylation of Ca2+-stimulated lysed platelets. A synergistic effect between these calpain antagonists and calmodulin antagonist W-7 was observed. Also, the similar results were obtained in 20K phosphorylation of intact platelets. From these observations, it was suggested that 20K phosphorylation in platelets is mediated by two separate pathways, namely calmodulin and calpain dependent pathways, provided that calpain activity is specifically inhibited by the antagonists used.