Intestinal Brush-border Membrane Transport of Monocarboxylic Acids Mediated by Proton-coupled Transport and Anion Antiport Mechanisms

Intestinal brush-border membrane transport of monocarboxylic acids was investigated by using rabbit intestinal brush-border membrane vesicles (BBMVs) and isolated intestinal tissues mounted on Ussing-type chambers. [³H]Mevalonic acid uptake by BBMVs showed an overshoot phenomenon in the presence of an inwardly directed proton gradient, but not in the presence of an inwardly directed sodium gradient or an outwardly directed HCO₃^? or chloride gradient. Initial uptake of mevalonic acid was saturable in the presence of a proton gradient. Uptake of [³H]mevalonic acid was inhibited by various monocarboxylic acids, including acetic acid, benzoic acid, lactic acid, nicotinic acid, pravastatin, salicylic acid and valproic acid, but not by dicarboxylic acid or amino acids. Acetic acid, which is transported by both anion antiport and proton-coupled transport systems, induced serosal bicarbonate-dependent alkalinization in the mucosal-side bathing solution of rabbit jejunal tissues, when examined in Ussing-type chambers. Pravastatin, which is a structural analogue of mevalonic acid and is absorbed via proton-coupled transport like mevalonic acid, did not. The result demonstrates that acetic acid is transported by the bicarbonate-dependent anion antiport system, whereas pravastatin is not. So, it is suggested that monocarboxylic acids are transported by at least two independent transporters, namely, a proton-coupled transporter for most monocarboxylic acids, including mevalonic acid, pravastatin and acetic acid, and an anion antiporter for acetic acid, but not for mevalonic acid or pravastatin. Activation of anion antiporter can induce HCO₃^? secretion in intact intestine.     

Tamoxifen Therapy for Premenopausal and Postmenopausal Japanese Females with Advanced Breast Cancer

The antiestrogenic agent tamoxifen was orally administered to74 Japanese patients with advanced breast cancer, with the followingresults: (1) Administration of tamoxifen resulted in a totalresponse rate of 43.4% (Marked response 23.0%, Moderate response20.3%), equivalent to 31.1% (Complete response + Partial response)by the criteria of the International Union against Cancer. (2)With regard to metastatic lesions, the response rate was 44.4%for soft tissue, 28.0% for skeletal, and 44.4% for pulmonaryand pleural metastases. (3) Tamoxifen induces very slight sideeffects compared to the commonly used androgens, and it hasno androgenic action. (4) Tamoxifen was shown to be effectivenot only in postmenopausal patients but also in pre menopausalpatients. (5) The appropriate dose of tamoxifen for Japanesepatients with advanced breast cancer is considered to be 20mg/day. (6) When patients with recurrent cancer were treated,many who responded to previous endocrine therapy or treatmentwith other anticancer drugs also responded well to tamoxifentherapy.     

Varicella infection complicated with meningitis after immunization

A healthy 45 month old boy who had received varicella vaccine 21 months previously developed aseptic meningitis along with an episode of varicella. The presence of viral DNA in cerebrospinal fluid (CSF) detected by polymerase chain reaction (PCR) with Southern blot hybridization confirmed the relationship between the symptoms and the CSF pleocytosis. This is the first reported case of this complication of varicella meningitis occurring in a child with documented immunization and seroconversion.     

Primary Adrenocortical Carcinoma and Ganglioneuroblastoma Followed by Rhabdomyosarcoma in a Child: A Case Report

We report a case of a young child affected by triple cancerswho developed a pleomorphic rhabdomyosarcoma of the retroperitoneumfollowing prophylactic chemotherapy after surgery for doubleprimary adrenocortical carcinoma and ganglioneuroblastoma. It is suggested that genetic susceptibility and chemotherapymight be responsible for the development of rhabdomyosarcomaas the second malignant neoplasm.     

Erratum

A heptadecapeptide has been isolated from a side fraction of β-MSH in an acid acetone extract of the pituitary of the salmon, Oncorhynchus keta. The sequence analysis revealed the peptide to be another form of salmon β-MSH with following primary structure; H-Asp-Gly-Ser-Tyr-Arg-Met-Gly-His-Phe-Arg-Trp-Gly-Ser-Pro-Thr-Ala-Ile-OH. The findings of two distinctive β-MSHs as well as two endorphins as reported previously in the pituitary extract suggest that the teleost pituitary may secrete two different precursor molecules, β-LPH, and thus also higher molecular weight precursors.     

Transthoracic Needle Biopsy for Lung Cancer

In the diagnosis of lung cancer, some lesions defy our routinemethods of sputum cytology and transbronchial lung biopsy, orcytology by using the bronchofiberscope; or under some circumstances,neither cytology nor histology by means of the bronchofiberscopecan possibly be applied. To obtain a definite diagnosis of suchcases the biopsy needle, 0.4 mm in diameter and 125 mm in length,has been developed. Since September 1969, transthoracic needlebiopsy has been performed on 276 thoracic lesions, consistingof 86 of lung cancer, 71 of metastatic lung tumors, 10 of malignantmediastinal tumors, and 109 of benign lesions, resulting ina positive diagnosis for all of the 86 lesions of lung cancer,of which 74 (86.0%) were of the peripheral type, and nine wereless than 2 cm. The complications following biopsy were 29 instancesof bloody sputum (10.5%) and 25 of pneumothorax (9.1%). Thoracicdrainage was used for eight patients but no tumor implantationwas observed, nor did any of the complications prove serious.From these results it is considered that transthoracic needlebiopsy, with its high degree of diagnostic accuracy, painlessnessand safety to the patient, simplicity and low cost may be ofgreat value in the diagnosis of lung cancer, especially of theperipheral type.     

Chemotherapy with Mitomycin-C and Cyclophosphamide Adjuvant to Surgery for Breast Cancer

The effect of adjuvant chemotherapy on breast cancer was studiedin two trials. In the first, mitomycin-C was administered intravenouslyto 203 patients and cyclophosphamide intravenously or orallyto 72 patients, within four weeks after radical mastectomy.The results were evaluated by compairing the recurrence-freerates of these patients with those of 556 patients who receivedsurgery alone. The effect of postsurgical adjuvant chemotherapy on the recurrence-freerate was statistically significantly better than that of surgeryalone when one or two axillary lymph nodes were involved inmetastasis, possibly because of the suppressive effect of chemotherapyon the establishment of hematogeneous metastases. With no orthree to seven metastases, the recurrence-free rate for patientsreceiving surgical treatment combined with adjuvant chemotherapywas higher than that for those with surgery alone, but the differencewas not statistically significant. In advanced cases havingeight or more axillary lymph node metastases, chemotherapy appearedsignificantly to reduce the recurrence- free rate compared withsurgery alone. This is possibly attributable to deteriorationin host immunity caused by chemotherapy being administered immediatelyafter surgery and affecting the host's defense mechanisms. In the second trial, which is still in progress, oral cyclophosphamidewas administered to 172 patients, 150 mg daily, for 34 daysfrom the seventh day after surgery. When compared with 179 patientshaving surgery alone, this chemotherapy increased the four-yearrecurrence-free rate in patients with no axillary lymph nodemetastases and the two-year recurrence-free rate in patientswith eight or more axillary lymph node metastases.     

Studies on the structure of a novel peptide antibiotic,K-582

A novel peptide antibiotic, K-582, which exhibited significant growth inhibition of Candida, viruses and ascites tumor in mice, was found in the culture medium of a strain of Metarhizium anisopliae by Kondo et al. (J. Antibiotics 33 , 535–542 (1980)]. K-582 consisted of two components, designated K-582 A and K-582 B. Threonine, tyrosine, ornithine, and an unusual amino acid were common in both peptides, but lysine was an extra component of K-582 A. The unusual amino acid was identified to be threo-γ-hydroxy-L-arginine (OHArg) by means of mass, nuclear magnetic resonance and infrared spectrometries of the derivatives and the related compounds. The threonine and the arginine were assigned to be L-configuration, and the ornithine and the tyrosine to be D-configuration in both K-582 A and K-582 B, and the lysine to be L-configuration by comparison of their optical rotatory dispersion spectra with those of standard amino acids. The elucidation of primary structure revealed that they were closely related heptapeptides with the following sequence: K-582 A:H-Arg-OHArg-Orn-Thr-Orn-Lys-Tyr-OH; K-582 B:H-Arg-OHArg-Orn-Thr-Orn-OHArg-Tyr-OH, and had the identical sequence in terms of the configuration of their constituents, namely L-L-D-L-D-L-D.     

Four Cases of T-Cell Malignancy in Childhood

Four cases of T-cell malignancy in childhood are reported. Inthe two older boys (seven [Case 1] and eight [Case 2] yearsold) the disease began as leukemia without a clinically detectablemediastinal mass. However, thymic involvement was found at autopsyin Case 1. Tumor cells of both patients had a rosetteformingcapacity with sheep erythrocytes (ERFC), high terminal deoxynucleotidyltransferase (TdT) activity and a positive acid phosphatase (AcPase)reaction. These findings suggest that the tumor cells of Cases1 and 2 originated from thymic T lymphocytes. The two younger patients (two [Case 3] and three [Case 4] yearsold) had cervical lymphadenopathy with mediastinal mass at onset,followed by leukemic change. The youngest patient (Case 3) lackedERFC and the AcPase reaction, but had C3 Receptor (C3-R), humanT-lymphocyte antigen (HLTA) and TdT activity. These findingsindicate that the tumor cells of Case 3 are compatible withearly thymic T lymphocytes. Tumor cells of Case 4 had ERFC,C3-R, HTLA, and slightly increased TdT activity. These findingssuggest that the tumor cells of Case 4 originated from thymicT lymphocytes. Only one patient has maintained an initial complete remissionfor more than one year. The three others relapsed or had a leukemicconversion within 12 months of the initial remission and twodied within 13 months. This indicates that childhood T-cellmalignancies have a poor prognosis.