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Biomedical subjects

M G Wood

Publications and source records attributed to M G Wood.

At least 19 recordsLinked to original sources

Assessment of plant chaperonin-60 gene function in Escherichia coli.

Brassica napus chaperonin-60 alpha and chaperonin-60 beta genes expressed separately and in combination produce three novel Escherichia coli strains: alpha, beta, and alpha beta. In beta and alpha beta cells, the plant gene products assemble efficiently into tetradecameric cpn60(14) species, including novel hybrids containing both bacterial and plant gene products. The levels of authentic groEL14 are reduced in these cells (Cloney, L. P., Wu, H. B., and Hemmingsen, S. M. (1992) J. Biol. Chem. 267, 23327-23332). The assembly of cyanobacterial ribulose-P2 carboxylase (rubisco) in E. coli requires the activities of the endogenous chaperonin proteins. Furthermore, the extent to which assembly occurs is limited by the normal levels of expression of the groE operon (Goloubinoff, P., Gatenby, A. A., and Lorimer, G. H. (1989) Nature 337, 44-47). We have now monitored the accumulation of cyanobacterial rubisco in E. coli alpha, beta, and alpha beta cells to assess the activity of the plant cpn60 gene products and effects on endogenous chaperonin functions. Expression of cpn-60 alpha alone did not enhance rubisco assembly, which is consistent with our previous observation that p60cpn-60 alpha required the presence of p60cpn-60 beta for assembly into cpn60(14) species. In contrast, expression of cpn-60 beta alone resulted in markedly enhanced rubisco assembly in cells that accumulated normal levels of both endogenous chaperonin polypeptides (groEL and groES). This demonstrates that assembled p60cpn-60 beta is functional as a chaperonin in E. coli. Co-expression of cpn-60 alpha and cpn-60 beta in cells with normal levels of expression of groES and groEL suppressed rubisco assembly. Increased expression of groES in cells in which cpn-60 alpha and cpn-60 beta were co-expressed relieved this suppression and resulted in enhanced rubisco assembly. Implications with respect to dependence of chloroplast cpn60 function on cpn10 are discussed.

Bacterial Proteins

Structure-activity relationship of synthetic branched-chain distearoylglycerol (distearin) as protein kinase C activators.

Several representative branched-chain analogues of distearin (DS) were synthesized and tested for their abilities to activate protein kinase C (PKC) and to compete for the binding of [3H]phorbol 12,13-dibutyrate (PDBu) to the enzyme. Substitutions of stearoyl moieties at sn-1 and sn-2 with 8-methylstearate decreased activities on these parameters, relative to those of the parental diacylglycerol DS, a weak PKC activator. Substitutions with 8-butyl, 4-butyl, or 8-phenyl derivatives, on the other hand, increased activities of the resulting analogues to levels comparable to those seen for diolein (DO), a diacylglycerol prototype shown to be a potent PKC activator. Kinetic analysis indicated that 8-methyldistearin (8-MeDS) acted by decreasing, whereas 8-butyldistearin (8-BuDS) and 8-phenyldistearin (8-PhDS) acted by increasing, the affinities of PKC for phosphatidylserine (PS, a phospholipid cofactor) and Ca2+ compared to the values seen in the absence or presence of DS. The stimulatory effect of 8-BuDS and 8-PhDS on PKC, as DO, was additive to that of 1,2-(8-butyl)distearoylphosphatidylcholine [1,2(8-Bu)DSPC] and, moreover, they abolished the marked inhibition of the enzyme activity caused by high concentrations of 1,2(8-Bu)DSPC. The present findings demonstrated a structure-activity relationship of the branched-chain DS analogues in the regulation of PKC, perhaps related to their abilities to specifically modify interactions of PKC with PS and/or Ca2+ critically involved in enzyme activation/inactivation.

Binding, Competitive

Synthetic branched-chain analogues of distearoylphosphatidylcholine: structure-activity relationship in inhibiting and activating protein kinase C.

A series of distearoylphosphatidylcholine (DSPC) analogues having various branched alkyl chains were synthesized and tested for their abilities to regulate protein kinase C (PKC). The greatest improvement (about 3-fold) in the PKC inhibitory activity over that seen for the parental lipid (i.e., DSPC) was accomplished by substitution of 8-methylstearate at sn-2 and 16-methylstearate at both sn-1 and sn-2 positions of glycerol; substitutions at both sn-1 and sn-2 with 8-methylstearate, on the other hand, caused a decrease (about 4-fold) in its inhibitory activity. Introduction of butyl, phenyl, or keto functions to various positions in the fatty alkyl chain substituted at both sn-1- and sn-2 positions imparted upon the DSPC analogues an ability to potently stimulate PKC to an extent comparable to those attainable by diacylglycerol or phorbol ester; the analogues having substitution only at the sn-2 position, in comparison, had no or reduced stimulatory activity. The butyl, phenyl, and keto analogues of DSPC, as with DSPC itself and its methyl analogues, inhibited PKC at high concentrations. Kinetic analysis indicated that the methyl DSPC analogues inhibited the enzyme competitively with respect to phosphatidylserine (PS; a phospholipid cofactor) and Ca2+. The butyl analogues activated the enzyme without affecting its affinity for PS or Ca2+, indicating a mechanism different from that seen for diacylglycerol or phorbol ester. The inhibitory activity of the methyl DSPC analogues and the stimulatory activity of the butyl DSPC analogues were reduced when PKC was activated by phorbol ester. Both classes of the analogues were unable to compete for the binding of [3H]phorbol dibutyrate to PKC.(ABSTRACT TRUNCATED AT 250 WORDS)

Calcium Chloride

Use of curettage and shave excision in office practice. Microscopic confirmation of removal.

The technic of curettage and shave excision can be learned by the general dermatologist as a useful office procedure. With its roots in Mohs' surgery, its chief characteristic is that it provides microscopic confirmation of complete removal. The procedure appears to have certain indications and definite limitations. An effort has been made to define these. In general, curettage and shave excision will be most useful as a substitute for curettage and electrodesiccation in locations and for skin cancers for which the curettage and electrodesiccation procedure is being considered but is not quite adequate. Nineteen cases are presented. They fall into two groups, according to the timing of the procedure. Although the technic is not difficult, it is more time consuming than curettage and electrodesiccation, and it requires much more attention to detail. The interpretation of horizontal sections presents certain pitfalls that must be recognized.

Adult

Malignant pilomatricoma.

An 86-year-old man had a tumor in the right posterior cervical region. The lesion showed histopathologic features of pilomatricoma but differed from that lesion by the presence of cytologically atypical cells and focal squamoid differentiation. The term "malignant pilomatricoma" is suggested for this tumor.

Aged

Subacute bacterial endocarditis presenting with necrotic skin lesions.

Classical lesions associated with subacute bacterial endocarditis include petechiae, splinter hemorrhages, Osler's modes and Janaway lesions. We describe a patient with subacute bacterial endocarditis, whose sole cutaneous findings were bullous necrotic lesions of the lower extremities. The superficial vessels were occluded by acidophilic material and coccal bacteria were identified in the vessels. Immunofluorescent studies revealed Igm and C3 in the vessel walls.

Adolescent

Intramucosal carcinoma of the gastric antrum complicating Menetrier's disease.

A 48-year-old man presented with haematemesis and was found to have Menetrier's disease. Three and a half years later early gastric cancer was detected at routine follow-up endoscopy. This is the first report of the development of early gastric cancer during follow-up in a case of Menetrier's disease. It is probable that patients with Menetrier's disease are at increased risk of gastric cancer, and should have regular endoscopic follow-up with gastric biopsy.

Gastric Mucosa

Acrokeratoelastoidosis.

Acrokeratoelastoidosis is a very rare entity of unknown etiology, characterized by small, firm, yellowish, translucent papules which usually appear on the margins of the hands and feet between the junction of the dorsal and palmar/plantar skin. Histologically, the most characteristic features are hyperkeratosis, mild acanthosis, and, most strikingly, fragmentation of coarse elastic fibers within the reticular dermis. This eruption is variable in terms of its onset, may be sporadic or familial, is generally asymptomatic, and has a prolonged course.

Acantholysis

Porokeratosis of Mibelli. A perforating disease of the epidermis.

A case of linear porokeratosis of Mibelli is presented. Although there was no suggestion clinically of a perforating disorder, histologic examination revealed a cornoid lamella penetrating into the dermis. Special stains did not show any evidence of a transepidermal elimination syndrome.

Female

Nodular superficial pigmented basal cell epitheliomas.

Eradication of multiple nodules, papules, and plaques of pigmented basal cell epitheliomas of the back of one patient was achieved by nine months of daily treatment with 5% fluorouracil cream. Such topical chemotherapy offers the physician an alternative to surgery and radiation in treating patients who have widespread nodular superficial epitheliomas. The need for a prolonged period of treatment and follow-up is emphasized.

Administration, Topical

Transformation of the common wart into squamous cell carcinoma in a patient with primary lymphedema.

A patient is reported in whom treatment-resistant periungual and subungual warts underwent malignant transformation into squamous cell carcinoma. Similar changes were observed in multiple warts of the vulvar, perianal, and intravaginal as well as cervical area. The tumors that develop were in many instances microinvasive but did not metastasize. The remarkable conversion of a common wart into a squamous cell carcinoma further implicates the human papovavirus in oncogenesis. The specific factors accountable for the malignant change remain completely unknown, but the patient's lymphedema praecox, as well as her severe reaction to vaccinia, and her development of a disseminate systemic Mycobacterium scrofulaceum infection suggest that the critical factor may be one of immunity.

Adult

Premalignant lymphoid hyperplasia preceding and coexisting with malignant lymphoma in the skin.

A primary malignant lymphoma of the skin had concurrent and antecedent lesions showing histologic changes of completely benign lymphoid hyperplasia. The malignant lymphoma itself evolved during a few years, although specimens from repeated biopsies had previously exhibited benign lymphoid hyperplasia. We urge that persistent benign lymphoid hyperplasia in its many clinical forms in the skin be recognized as a long-term premalignant lesion. Awareness of such a continuum of benign to malignant change aids in the interpretation of the histologic findings in these growths and alerts the clinician to the need for years of careful surveillance. Histologic assessment should indicate whether the specimen shows benign, indeterminate, or malignant change.

Female