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Biomedical subjects

M Lai

Publications and source records attributed to M Lai.

At least 127 records · Page 7Linked to original sources

Effect of intestinal bypass on the expression of actin mRNA in ileal smooth muscle.

In this study, messenger RNAs (mRNAs) for actin isoforms were assessed in longitudinal smooth muscle from the ileum of unoperated rats and from rats that had undergone bypass of the middle 70% of the small intestine. The plasmid clone pGEM 10C, which contains a DNA insert complementary to the 3' untranslated region and the region of mRNA that codes for the synthesis of alpha-smooth muscle actin protein, was used to synthesize two riboprobes. One probe, complementary to the coding region of the insert, hybridizes to most, if not all, actin isoform mRNAs. The second probe, complementary to the 3' untranslated region of the insert, hybridizes only to alpha-smooth muscle actin mRNA. RNA was isolated from animals 4 to 5 days after operation, size fractionated by denaturing gel electrophoresis, transferred to nylon membranes, and exposed to the two 32P-labeled riboprobes. Both probes hybridized to RNA of about 1.3 kilobases long. Longitudinal muscle from both groups of animals contained alpha-smooth muscle actin mRNA as well as mRNA for other actin isoforms. Dot blots of varying amounts of RNA were hybridized to the riboprobes to determine the proportions of actin mRNAs. The content and concentration of mRNAs for all actins, and of mRNA for alpha-smooth muscle actin, were significantly greater in muscle from the functioning ileum of bypassed animals 4-5 days after the operation. Thus the operation induces a rapid, specific activation of these contractile protein genes.

Actins↗

Rearrangement of the breakpoint cluster region in Philadelphia chromosome positive acute leukemia.

The rearrangement of breakpoint cluster region (ber) was examined in leukemic cells obtained from 3 patients initially diagnosed as having Ph+ acute leukemia, 2 with acute lymphocytic leukemia (ALL) and one with acute mixed leukemia. DNA was digested with Bgl II and BamH I. The ber rearrangement was present in the case of acute mixed leukemia (Case 1), but was absent in the 2 cases of ALL (Cases 2 and 3). These results suggest that Case 1 represented a type of blast crisis of chronic myelocytic leukemia which was unusual in the sense of the occurrence of a myeloid-lymphoid conversion and lack of an apparent chronic phase. Cases 2 and 3 appeared to be de novo Ph+ ALL.

Blast Crisis↗

The correlation between the spread of metastases by level in the axillary nodes and disease-free survival in breast cancer. A multifactorial analysis.

Axillary lymph nodes were separated from 492 radical or modified radical mastectomies for primary breast cancer and examined according to their anatomical level corresponding to their position along the theoretical pathway of lymph drainage from the breast. The patterns of metastasis and the relationship between metastatized levels and disease-free survival were investigated to see whether complete axillary dissection is necessary for the staging and the planning of adjuvant therapy in breast cancer. Progressive involvement from level I (proximal) to level III (distal) was found in 206 specimens (80.8% of tumors with axillary metastases), while discontinuous or "skip" metastases were present in 49 (19.2%), including 38 (14.9%) with positive nodes at level II or III but not at level I. "Skip" metastasis was more frequent when fewer than four nodes were positive, and not related to either the size of the primary tumor or its location. The effect of age, menopausal status, tumor size, node status, number of positive nodes, anatomic level of axillary node involvement, estrogen and progesterone receptors, and adjuvant therapies on disease-free survival was evaluated using a multivariate proportional hazard model and life table analysis. This showed that disease-free survival was strongly related to the number of positive nodes (P less than 0.001), tumor size (P = 0.001) and level of node involvement (P = 0.01) as independent prognostic factors. Moreover, the subset of patients with four or more positive nodes and involvements of level III had a higher risk of recurrence (25% recurrence-free patients 5 years after mastectomy). The high frequency of "skip" metastases and the prognostic value of both the level of involvement and the number of metastatic nodes suggest that a complete axillary dissection is needed in the surgical management of breast cancer to obtain all the data useful in the planning of adjuvant therapy.

Axilla↗

Development of autonomously replicating plasmids for Candida albicans.

A pool of Candida albicans RsaI fragments cloned onto a vector containing pBR322 sequences and the Candida ADE2 gene was used to transform a Candida ade2 mutant to adenine protrophy. A potential autonomously replicating sequence (ARS) in Candida DNA was identified by two criteria: instability of the selectable marker in the absence of selection and the presence of free plasmid in total DNA preparations. Plasmids carrying the ARS transformed C. albicans at a high frequency (200 to 1,000 ADE+ transformants per microgram of DNA), and Southern hybridization analysis of these transformants indicated that multiple copies of the plasmid sequences were present and that, although they were present in high-molecular-weight molecules, these sequences had not undergone rearrangement. Orthogonal field alternation gel electrophoresis indicated that the high-molecular-weight transforming sequences were not associated with any chromosome. The simplest interpretation to account for these data is that the transforming sequences are present as oligomers consisting of head-to-tail tandem repeats. The transformed strains occasionally yield stable segregants in which the transforming sequences are integrated into the chromosome as repeats. The Candida sequence responsible for the ARS phenotype was limited to a single 0.35-kilobase RsaI fragment which is present in one copy per haploid genome.

Candida albicans↗

The influence of hormone receptors and hormonal adjuvant therapy on disease-free survival in breast cancer: a multifactorial analysis.

The prognostic value of estrogen (ER) and progesterone (PgR) receptor status and the influence of hormonal adjuvant therapy on disease-free survival (DFS) in breast cancer were evaluated in 680 women after radical and modified radical mastectomy. The effect of 17 variables, including clinical data, TNM, hormone receptor status, histology and adjuvant therapy, on the DFS observed was analyzed, using a multivariate proportional hazard model. Multifactorial analysis revealed that DFS was strongly related to the number of positive axillary nodes (P less than 0.001) and the histological grade of the tumor (P = 0.05). Moreover, the DFS of ER-positive patients with node involvement was significantly improved by hormonal adjuvant therapy (tamoxifen). Combination of adjuvant chemotherapy with hormonal therapy did not enhance its effectiveness. Recurrence rates of either node-negative or ER-negative patients were not affected by either adjuvant therapy. When no systemic therapy was given, no significant relationship between ER or PgR content of the tumor and the DFS was observed. These findings suggest that hormone receptor status is not an independent prognostic factor but provides reliable information on responsiveness to adjuvant hormonal therapy which is very effective in patients selected on the basis of ER assay.

Adult↗

Dissociation of adrenal androgen and cortisol levels in acute stress.

Patients recovering from acute surgical stress often excrete increased 17-OH corticosteroids with no change in 17-ketosteroids. The explanation for these findings is unclear. In order to investigate possible divergence between cortisol and adrenal androgen metabolism in acute stress, repeated morning cortisol and dehydroepiandrosterone (DHA) measurements were made in patients undergoing ACTH stimulation 48 to 96 hours preoperatively, followed by determinations before and during major surgery, also performed in the morning. Cortisol and DHA are largely metabolized by the liver, so liver blood flow under a constant general anesthetic regimen known not to affect cortisol metabolism was monitored by pre- and intraoperative indocyanine green dye clearance. Results indicated no difference between the cortisol and DHA stimulation resulting from two hours of ACTH stimulation or major surgery, and a small (14.4%) decline in hepatic blood flow during general anesthesia. However, while DHA concentrations remained constant immediately preceding surgery, cortisol concentrations increased by 61% (P less than 0.05). Previous studies have also demonstrated increased concentrations of cortisol before surgical procedures, presumably due to psychological stress. However, this is the first demonstration of a dissociation between concentrations of cortisol and an adrenal androgen due to psychological stress.

Adrenal Glands↗

The correlation between estrogen and progesterone receptors and some clinical and pathological features in human breast cancer.

The correlation between estrogen (ER) and progesterone (PgR) receptor status and some clinical and pathological features was evaluated in a series of 680 breast carcinomas. ER status was significantly related to age, menopause, histological grade and vascular invasion. No relationship was found with tumor size, lymph node involvement, histotype and multicentricity. PgR status was significantly related to vascular invasion only. Despite the relationship between ER and favorable pathological features, ER-positive patients did not show a longer disease-free interval after surgery when no systemic adjuvant therapy was administered. ER status is thus of little prognostic value.

Adult↗

Orchiectomy does not selectively increase adrenal androgen concentrations.

Prostatic carcinoma is androgen dependent and, therefore, treated by orchiectomy. However, adrenal androgen secretion remains intact after orchiectomy, and several investigators even reported an increase in serum adrenal androgen concentrations after orchiectomy. Such an increase in androgen secretion theoretically could promote tumor recurrence. To investigate this question, we obtained multiple blood samples from 10 men before, within 1 week after, and up to 6 months after orchiectomy for prostatic carcinoma. Serum testosterone concentrations became unmeasurable (less than 40 ng/dl) after orchiectomy. Three of the 10 patients had transient increases of at least 50% in both serum dehydroepiandrosterone (DHA) and cortisol after orchiectomy, presumably due to surgical stress, but mean serum DHA and DHA sulfate (DHAS) did not increase in the group as a whole. Subsequently, serum DHA and DHAS concentrations were similar to preoperative values in all patients. Therefore, we find no evidence to support the hypothesis that adrenal androgen concentrations increase after orchiectomy.

Adrenal Glands↗

Interaction between human lymphoblastoid interferon and chemotherapeutic agents in vitro.

The combined effect of human lymphoblastoid interferon (HLBI) and anticancer agents on the growth of MOLT-4 was studied in vitro. The interferon showed a strikingly synergistic interaction in combination with aclarubicin, cytosine arabinoside or prednisolone. It was moderately synergistic in combination with adriamycin or 5-fluorouracil and tended to show additive effects with daunorubicin or vincristine. In vitro studies of combination chemotherapy with interferon and anticancer agents should yield valuable information as to the best combination for man.

Antineoplastic Agents↗

[Effects of interferon and its inducers on neutrophil chemiluminescence].

In order to evaluate effects of interferon (IFN) and its inducers on neutrophil functions, neutrophil chemiluminescence (ChL) was assayed in 12 patients treated with IFN (human lymphoblastoid interferon, 3.0 X 10(6) units/day i.m. daily) or Ge-132 (2,250 mg/day p.o. daily). The peak levels of neutrophil ChL, assayed one week after the initiation of treatment, were increased in comparison to those before treatment, but one month after treatment they were decreased to pretreatment levels in spite of the daily administration of the agent. On the basis of these results, it was concluded that IFN and Ge-132 enhanced the host defence mechanism including the activation of neutrophils, which appeared at the early phase of the host reaction.

Adenocarcinoma↗

Carbon tetrachloride, bromotrichloromethane and ethanol acute intoxication. New chemical evidence for lipid peroxidation in rat tissue microsomes.

Second-derivative spectroscopy was used to determine the conjugated-diene shift that measures the extent of the first step of lipid peroxidation after carbon tetrachloride (CCl4), bromotrichloromethane (BrCCl3) and ethanol intoxication. The conjugated-diene signal was recorded in the second-derivative spectra as a minimum peak at 233 nm. The use of this method enabled us to show that, under our experimental conditions, CCl4- and BrCCl3-dependent conjugated-diene formation in rat liver microsomes is not dose-dependent and increases linearly with time up to 3h. Proportionality was not obtained between the second-derivative-spectroscopy method, and the thiobarbituric acid and difference-spectra methods. In addition, whereas the thiobarbituric acid and difference-spectra methods gave positive results at zero time, second-derivative spectroscopy showed no evidence of formation of conjugated dienes under the same experimental conditions. Intoxication with ethanol was shown by the appearance of the conjugated-diene signal in liver microsomes 24 h after the administration of the toxin. Intoxication with either of the haloalkanes or ethanol did not give rise to any similar peak in lung and brain microsomes. The results obtained are discussed.

Animals↗

[Clinical effects of ceftizoxime and latamoxef on infections in acute leukemia].

Ceftizoxime (CZX) and latamoxef (LMOX), new synthetic cephems, are stable against various types of beta-lactamase and highly active against Gram-negative rods, such as H. influenzae, Serratia, Enterobacter and indole (+) Proteus. In this study, we evaluated clinical effects of CZX and LMOX in the clinical management of infections in acute leukemia. Sixteen episodes of infections were treated with CZX or LMOX. Four causative organisms, P. aeruginosa, S. faecalis, K. pneumoniae and A. faecalis, were identified in 2 episodes of infections. Clinical effects were recognized at 75% in 8 episodes treated with CZX and at 71% in 7 episodes treated with LMOX, respectively. The transient evaluation of GOT, GPT and Al-P, recognized in several cases. In conclusion, the clinical effects of CZX and LMOX are promised in clinical management of infections in acute leukemia.

Acute Disease↗